{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:03:34Z","timestamp":1793678614578,"version":"4.5.1"},"reference-count":262,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>CRISPR\/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing and modulation of gene function with an unparalleled precision and effectiveness. Among the various applications and prospects of this technology, the opportunities it offers in unraveling the molecular underpinnings of a myriad of central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, and developmental abnormalities, are unprecedented. In this review, we highlight the applications of CRISPR\/Cas9-based therapeutics as a promising strategy for management of Alzheimer\u2019s disease and transformative impact of this technology on AD research. Further, we emphasize the role of CRISPR\/Cas9 in generating accurate AD models for identification of novel therapeutic targets, besides the role of CRISPR-based therapies aimed at correcting AD-associated mutations and modulating the neurodegenerative processes. Furthermore, various delivery systems are reviewed and potential of the non-viral nanotechnology-based carriers for overcoming the critical limitations of effective delivery systems for CRISPR\/Cas9 is discussed. Overall, this review highlights the promise and prospects of CRISPR\/Cas9 technology for unraveling the intricate molecular processes underlying the development of AD, discusses its limitations, ethical concerns and several challenges including efficient delivery across the BBB, ensuring specificity, avoiding off-target effects. This article can be helpful in better understanding the applications of CRISPR\/Cas9 based therapeutic approaches and the way forward utilizing enormous potential of this technology in targeted, gene-specific treatments that could change the trajectory of this debilitating and incurable illness.<\/jats:p>","DOI":"10.3389\/fncel.2025.1578138","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T01:32:28Z","timestamp":1743989548000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["CRISPR\/Cas9-Based therapeutics as a promising strategy for management of Alzheimer\u2019s disease: progress and prospects"],"prefix":"10.3389","volume":"19","author":[{"given":"Mohamad Sultan","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nousheen","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehan","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ok","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Maqbool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1038\/s41467-018-04252-2","article-title":"The CRISPR tool kit for genome editing and beyond.","volume":"9","author":"Adli","year":"2018","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"101533","DOI":"10.1016\/j.jddst.2020.101533","article-title":"Nanoparticles-mediated CRISPR\/Cas9 delivery: Recent advances in cancer treatment.","volume":"56","author":"Aghamiri","year":"2020","journal-title":"J. Drug Deliv. Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.3233\/JAD-170634","article-title":"Co-localization of glia maturation factor with NLRP3 inflammasome and autophagosome markers in human Alzheimer\u2019s disease brain.","volume":"60","author":"Ahmed","year":"2017","journal-title":"J. Alzheimers Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"102289","DOI":"10.1016\/j.arr.2024.102289","article-title":"Types of memory, dementia, Alzheimer\u2019s disease, and their various pathological cascades as targets for potential pharmacological drugs.","volume":"96","author":"Akhtar","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6057","DOI":"10.1111\/ejn.16541","article-title":"Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis, and Huntington\u2019s disease.","volume":"60","author":"Akyuz","year":"2024","journal-title":"Eur. J. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13041-022-00937-4","article-title":"Blood-brain barrier: Emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders.","volume":"15","author":"Alajangi","year":"2022","journal-title":"Mol. Brain."},{"key":"B7","doi-asserted-by":"publisher","first-page":"111","DOI":"10.14715\/cmb\/2025.70.1.12","article-title":"Alzheimer\u2019s disease: Assessing the therapeutic potential of anti-A\u03b2 (Beta-Amyloid) treatments.","volume":"71","author":"Almutairi","year":"2025","journal-title":"Cell. Mol. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.3390\/ijms24043754","article-title":"Alzheimer\u2019s disease: An updated overview of its genetics.","volume":"24","author":"Andrade-Guerrero","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA.","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0079-6123(04)47025-3","article-title":"Alzheimer\u2019s disease as a disorder of dynamic brain self-organization.","volume":"147","author":"Arendt","year":"2005","journal-title":"Prog. Brain Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"102620","DOI":"10.1016\/j.arr.2024.102620","article-title":"Monoclonal therapy with lecanemab in the treatment of mild Alzheimer\u2019s disease: A systematic review and meta-analysis.","volume":"104","author":"Arroyo-Pacheco","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s004010100423","article-title":"Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer\u2019s disease.","volume":"103","author":"Augustinack","year":"2002","journal-title":"Acta Neuropathol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"12495","DOI":"10.3390\/ijerph191912495","article-title":"Neurodegenerative diseases: Implications of environmental and climatic influences on neurotransmitters and neuronal hormones activities.","volume":"19","author":"Ayeni","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1124\/jpet.114.219352","article-title":"Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer\u2019s disease.","volume":"352","author":"Baddeley","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B15","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s40120-020-00218-z","article-title":"CRISPR\/Cas9: A promising genome editing therapeutic tool for Alzheimer\u2019s disease\u2014A narrative review.","volume":"9","author":"Barman","year":"2020","journal-title":"Neurol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1212\/01.wnl.0000065892.67099.2a","article-title":"Gender, cognitive decline, and risk of AD in older persons.","volume":"60","author":"Barnes","year":"2003","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.coi.2014.12.008","article-title":"The roles of CRISPR\u2013Cas systems in adaptive immunity and beyond.","volume":"32","author":"Barrangou","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1126\/science.1138140","article-title":"CRISPR provides acquired resistance against viruses in prokaryotes.","volume":"315","author":"Barrangou","year":"2007","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.molcel.2014.03.011","article-title":"CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.","volume":"54","author":"Barrangou","year":"2014","journal-title":"Mol. Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/S1474-4422(12)70259-4","article-title":"Genetic insights in Alzheimer\u2019s disease.","volume":"12","author":"Bettens","year":"2013","journal-title":"Lancet Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jare.2021.07.001","article-title":"CRISPR\/Cas9 gene editing: New hope for Alzheimer\u2019s disease therapeutics.","volume":"40","author":"Bhardwaj","year":"2022","journal-title":"J. Adv. Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13024-021-00443-6","article-title":"The CD33 short isoform is a gain-of-function variant that enhances A\u03b2 1\u201342 phagocytosis in microglia.","volume":"16","author":"Bhattacherjee","year":"2021","journal-title":"Mol. Neurodegener"},{"key":"B23","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s42003-019-0698-6","article-title":"Repression of phagocytosis by human CD33 is not conserved with mouse CD33.","volume":"2","author":"Bhattacherjee","year":"2019","journal-title":"Commun. Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"16084","DOI":"10.1038\/nrdp.2016.84","article-title":"Traumatic brain injuries.","volume":"2","author":"Blennow","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B25","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nrneurol.2010.4","article-title":"Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.","volume":"6","author":"Blennow","year":"2010","journal-title":"Nat. Rev. Neurol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e17578","DOI":"10.7554\/eLife.17578","article-title":"The amyloid-beta forming tripeptide cleavage mechanism of \u03b3-secretase.","volume":"5","author":"Bolduc","year":"2016","journal-title":"eLife"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12015-025-10857-0","article-title":"Applications of gene editing and nanotechnology in stem cell-based therapies for human diseases.","volume":"21","author":"Bolideei","year":"2025","journal-title":"Stem Cell Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nrn2620","article-title":"Apolipoprotein E and its receptors in Alzheimer\u2019s disease: Pathways, pathogenesis and therapy.","volume":"10","author":"Bu","year":"2009","journal-title":"Nat. Rev. Neurosci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/ddr.22085","article-title":"Targeting \u03b17 nicotinic acetylcholine receptors and their protein interactions in Alzheimer\u2019s disease drug development.","volume":"84","author":"Burns","year":"2023","journal-title":"Drug Dev. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1465871","DOI":"10.3389\/fnagi.2024.1465871","article-title":"Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer\u2019s disease: A systematic review and network meta-analysis of randomized controlled trials.","volume":"16","author":"Cai","year":"2025","journal-title":"Front. Aging Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s11481-019-09856-z","article-title":"Cas9 ribonucleoprotein complex delivery: Methods and applications for neuroinflammation.","volume":"14","author":"Campbell","year":"2019","journal-title":"J. Neuroimmune Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/ng.305","article-title":"Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer\u2019s disease.","volume":"41","author":"Carrasquillo","year":"2009","journal-title":"Nat. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"103652","DOI":"10.1016\/j.drudis.2023.103652","article-title":"CRISPER\/Cas9 in Alzheimer\u2019s disease: Therapeutic trends, modalities, and challenges.","volume":"28","author":"Chacko","year":"2023","journal-title":"Drug Discov. Today"},{"key":"B34","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","article-title":"Identification of preexisting adaptive immunity to Cas9 proteins in humans.","volume":"25","author":"Charlesworth","year":"2019","journal-title":"Nat. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1038\/emboj.2012.79","article-title":"The mechanism of \u03b3-secretase dysfunction in familial Alzheimer disease.","volume":"31","author":"Ch\u00e1vez-Guti\u00e9rrez","year":"2012","journal-title":"EMBO J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12943-023-01925-5","article-title":"Comprehensive review of CRISPR-based gene editing: Mechanisms, challenges, and applications in cancer therapy.","volume":"23","author":"Chehelgerdi","year":"2024","journal-title":"Mol. Cancer"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6634","DOI":"10.18632\/aging.202501","article-title":"CRISPR\/Cas9-mediated CysLT1R deletion reverses synaptic failure, amyloidosis and cognitive impairment in APP\/PS1 mice.","volume":"13","author":"Chen","year":"2021","journal-title":"Aging"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development.","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin"},{"key":"B39","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.canlet.2019.01.017","article-title":"CRISPR-Cas9 for cancer therapy: Opportunities and challenges.","volume":"447","author":"Chen","year":"2019","journal-title":"Cancer Lett."},{"key":"B40","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41576-022-00541-1","article-title":"Prime editing for precise and highly versatile genome manipulation.","volume":"24","author":"Chen","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/cr.2014.167","article-title":"Germline acquisition of Cas9\/RNA-mediated gene modifications in monkeys.","volume":"25","author":"Chen","year":"2015","journal-title":"Cell Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1093\/brain\/awaa045","article-title":"In vivo CRISPRa decreases seizures and rescues cognitive deficits in a rodent model of epilepsy.","volume":"143","author":"Colasante","year":"2020","journal-title":"Brain"},{"key":"B43","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s41582-023-00883-2","article-title":"Tau-targeting therapies for Alzheimer disease: Current status and future directions.","volume":"19","author":"Congdon","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1038\/s41467-018-05843-9","article-title":"Cas9 immunity creates challenges for CRISPR gene editing therapies.","volume":"9","author":"Crudele","year":"2018","journal-title":"Nat. Commun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.pneurobio.2018.04.008","article-title":"In vivo methods for acute modulation of gene expression in the central nervous system.","volume":"168","author":"Cwetsch","year":"2018","journal-title":"Prog. Neurobiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.2147\/NDT.S125620","article-title":"Biomarkers in traumatic brain injury (TBI): A review.","volume":"14","author":"Dadas","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"B47","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41582-025-01062-1","article-title":"The impact of rare genetic variants on Alzheimer disease.","volume":"21","author":"De Deyn","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"8714","DOI":"10.3390\/ijms23158714","article-title":"Applications of CRISPR-Cas9 in Alzheimer\u2019s disease and related disorders.","volume":"23","author":"De Plano","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1212\/01.wnl.0000263132.99055.0d","article-title":"CIND and MCI in the Italian elderly: Frequency, vascular risk factors, progression to dementia.","volume":"68","author":"Di Carlo","year":"2007","journal-title":"Neurology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1080\/03639040802020536","article-title":"CNS disorders\u2014current treatment options and the prospects for advanced therapies.","volume":"34","author":"DiNunzio","year":"2008","journal-title":"Drug Dev. Ind. Pharm"},{"key":"B51","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/978-1-61779-533-6_4","article-title":"Using lentiviral vectors as delivery vehicles for gene therapy","author":"Dissen","year":"2012","journal-title":"Controlled Genetic Manipulations"},{"key":"B52","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/sj.gt.3302222","article-title":"Delivery of GDNF by an E1, E3\/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson\u2019s disease.","volume":"11","author":"Do Thi","year":"2004","journal-title":"Gene Ther"},{"key":"B53","doi-asserted-by":"publisher","first-page":"952","DOI":"10.2174\/1567205013666160314150501","article-title":"Molecular basis of familial and sporadic Alzheimer\u2019s disease.","volume":"13","author":"Dorszewska","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"Genome editing. The new frontier of genome engineering with CRISPR-Cas9.","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1038\/s41598-021-82658-7","article-title":"Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer\u2019s disease model.","volume":"11","author":"Duan","year":"","journal-title":"Sci. Rep."},{"key":"B56","doi-asserted-by":"publisher","first-page":"673286","DOI":"10.3389\/fgene.2021.673286","article-title":"Nanoparticle delivery of CRISPR\/Cas9 for genome editing.","volume":"12","author":"Duan","year":"","journal-title":"Front. Genet."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1038\/s41598-025-86645-0","article-title":"A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease.","volume":"15","author":"Ehn","year":"2025","journal-title":"Sci. Rep."},{"key":"B58","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/j.stemcr.2023.02.002","article-title":"The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.","volume":"18","author":"Elamin","year":"2023","journal-title":"Stem Cell Rep."},{"key":"B59","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.semcdb.2020.02.005","article-title":"Contribution of the presenilins in the cell biology, structure and function of \u03b3-secretase, in Semin.","volume":"105","author":"Escamilla-Ayala","year":"2020","journal-title":"Cell Dev. Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00401-019-02000-4","article-title":"Evaluation of CD33 as a genetic risk factor for Alzheimer\u2019s disease.","volume":"138","author":"Estus","year":"2019","journal-title":"Acta Neuropathol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.biocel.2010.08.017","article-title":"BACE: Therapeutic target and potential biomarker for Alzheimer\u2019s disease.","volume":"42","author":"Evin","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neulet.2006.06.072","article-title":"Chinese presenilin-1 V97L mutation enhanced A\u03b242 levels in SH-SY5Y neuroblastoma cells.","volume":"406","author":"Fang","year":"2006","journal-title":"Neurosci. Lett"},{"key":"B63","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.pneurobio.2012.03.005","article-title":"Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia.","volume":"97","author":"Ferrer","year":"2012","journal-title":"Prog. Neurobiol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3","DOI":"10.17879\/freeneuropathology-2022-3806","article-title":"Alzheimer\u2019s disease is an inherent, natural part of human brain aging: An integrated perspective.","volume":"3","author":"Ferrer","year":"2022","journal-title":"Free Neuropathol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e13122","DOI":"10.1111\/bpa.13122","article-title":"Hypothesis review: Alzheimer\u2019s overture guidelines.","volume":"33","author":"Ferrer","year":"2023","journal-title":"Brain Pathol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1093\/brain\/awad024","article-title":"Tilavonemab in early Alzheimer\u2019s disease: Results from a phase 2, randomized, double-blind study.","volume":"146","author":"Florian","year":"2023","journal-title":"Brain"},{"key":"B67","doi-asserted-by":"publisher","first-page":"8913","DOI":"10.1073\/pnas.1207022109","article-title":"Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer\u2019s disease.","volume":"109","author":"Frieden","year":"2012","journal-title":"Proc. Natl Acad. Sci. U. S. A"},{"key":"B68","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/mt.2015.151","article-title":"Genome engineering using adeno-associated virus: Basic and clinical research applications.","volume":"24","author":"Gaj","year":"2016","journal-title":"Mol. Ther"},{"key":"B69","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1212\/01.wnl.0000132523.27540.81","article-title":"Mild cognitive impairment, amnestic type: An epidemiologic study.","volume":"63","author":"Ganguli","year":"2004","journal-title":"Neurology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jconrel.2018.05.008","article-title":"Drug delivery challenges and future of chemotherapeutic nanomedicine for glioblastoma treatment.","volume":"281","author":"Ganipineni","year":"2018","journal-title":"J. Control. Release"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5214\/ans.0972.7531.1118101","article-title":"Gamma-secretase activating protein is a therapeutic target for Alzheimer\u2019s disease: A path-breaking discovery finally paving way towards therapeutic intervention.","volume":"18","author":"Ghosh","year":"2011","journal-title":"Ann. Neurosci"},{"key":"B72","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/1535676019899502","article-title":"Viral vector systems for gene therapy: A comprehensive literature review of progress and biosafety challenges.","volume":"25","author":"Ghosh","year":"2020","journal-title":"Appl. Biosaf."},{"key":"B73","doi-asserted-by":"publisher","first-page":"665","DOI":"10.2147\/CIA.S105769","article-title":"Genes associated with Alzheimer\u2019s disease: An overview and current status.","volume":"11","author":"Giri","year":"2016","journal-title":"Clin. Interv. Aging"},{"key":"B74","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.tibtech.2017.11.006","article-title":"Engineering the delivery system for CRISPR-based genome editing.","volume":"36","author":"Glass","year":"2018","journal-title":"Trends Biotechnol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.jconrel.2024.11.008","article-title":"Enhanced CRISPR-Cas9 RNA system delivery using cell penetrating peptides-based nanoparticles for efficient in vitro and in vivo applications.","volume":"376","author":"Gonzalez","year":"2024","journal-title":"J. Control. Release"},{"key":"B76","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41583-018-0054-8","article-title":"Rodent models for Alzheimer disease.","volume":"19","author":"Gotz","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"a024117","DOI":"10.1101\/cshperspect.a024117","article-title":"Clinical spectrum of amyotrophic lateral sclerosis (ALS).","volume":"7","author":"Grad","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1038\/mt.2011.72","article-title":"Preclinical differences of intravascular AAV9 delivery to neurons and glia: A comparative study of adult mice and nonhuman primates.","volume":"19","author":"Gray","year":"2011","journal-title":"Mol. Ther."},{"key":"B79","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuropharm.2016.03.021","article-title":"The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes.","volume":"120","author":"Gribkoff","year":"2017","journal-title":"Neuropharmacology"},{"key":"B80","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.neuron.2013.04.014","article-title":"Alzheimer\u2019s disease risk gene CD33 inhibits microglial uptake of amyloid beta.","volume":"78","author":"Griciuc","year":"2013","journal-title":"Neuron"},{"key":"B81","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2174\/1566523034578285","article-title":"From virus evolution to vector revolution: Use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors for human gene therapy.","volume":"3","author":"Grimm","year":"2003","journal-title":"Curr. Gene Ther."},{"key":"B82","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1007\/s12035-021-02638-w","article-title":"CRISPR-Cas9-mediated gene therapy in neurological disorders.","volume":"59","author":"Guan","year":"2022","journal-title":"Mol. Neurobiol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"17306","DOI":"10.1074\/jbc.H118.006147","article-title":"A peptide delivery system sneaks CRISPR into cells.","volume":"293","author":"Guan","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B84","doi-asserted-by":"publisher","first-page":"4508","DOI":"10.3390\/ijms23094508","article-title":"Pathophysiological features of nigral dopaminergic neurons in animal models of Parkinson\u2019s disease.","volume":"23","author":"Guatteo","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.omtn.2021.02.032","article-title":"Base editing strategy for insertion of the A673T mutation in the APP gene to prevent the development of AD in vitro.","volume":"24","author":"Guyon","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B86","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.omtn.2018.03.007","article-title":"CRISPR\/Cas9 mediated disruption of the Swedish APP allele as a therapeutic approach for early-onset Alzheimer\u2019s disease.","volume":"11","author":"Gy\u00f6rgy","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B87","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s13195-020-00686-3","article-title":"\u03b2-Secretase1 biological markers for Alzheimer\u2019s disease: State-of-art of validation and qualification.","volume":"12","author":"Hampel","year":"2020","journal-title":"Alzheimers Res. Ther"},{"key":"B88","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3390\/pharmaceutics12090801","article-title":"CRISPR\/Cas9 delivery potentials in Alzheimer\u2019s disease management: A mini review.","volume":"12","author":"Hanafy","year":"2020","journal-title":"Pharmaceutics"},{"key":"B89","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease.","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"26224","DOI":"10.1073\/pnas.1912954116","article-title":"Alzheimer\u2019s disease: A clinical perspective and future nonhuman primate research opportunities.","volume":"116","author":"Haque","year":"2019","journal-title":"Proc. Natl Acad. Sci. U. S. A"},{"key":"B91","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nature09325","article-title":"Gamma-secretase activating protein is a therapeutic target for Alzheimer\u2019s disease.","volume":"467","author":"He","year":"2010","journal-title":"Nature"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census.","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"B93","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-med-051022-043645","article-title":"Lessons learned from approval of aducanumab for Alzheimer\u2019s disease.","volume":"75","author":"Heidebrink","year":"2024","journal-title":"Annu. Rev. Med."},{"key":"B94","doi-asserted-by":"publisher","first-page":"627494","DOI":"10.3389\/fncel.2020.627494","article-title":"Hot topics in cellular neuropathology.","volume":"14","author":"Hermann","year":"2020","journal-title":"Front. Cell. Neurosci"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1276077","DOI":"10.3389\/fncel.2023.1276077","article-title":"Hot topics in cellular neuropathology III: Using CRISPR\/Cas9 technology for deciphering central nervous system disease targets.","volume":"17","author":"Hermann","year":"2023","journal-title":"Front. Cell. Neurosci"},{"key":"B96","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1089\/hum.2016.087","article-title":"Adeno-associated virus-based gene therapy for CNS diseases.","volume":"27","author":"Hocquemiller","year":"2016","journal-title":"Hum. Gene Ther"},{"key":"B97","first-page":"547","author":"Hooli","year":"2016","journal-title":"The Genetic Basis of Alzheimer\u2019s Disease: Findings from Genome-Wide Studies, in Genomics, Circuits, and Pathways in Clinical Neuropsychiatry."},{"key":"B98","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.cell.2016.12.044.","article-title":"ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and A\u03b2 secretion.","volume":"168","author":"Huang","year":"2017","journal-title":"Cell"},{"key":"B99","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1016\/j.celrep.2018.11.095.","article-title":"Altered \u03b3-secretase processing of APP disrupts lysosome and autophagosome function in monogenic Alzheimer\u2019s disease.","volume":"25","author":"Hung","year":"2018","journal-title":"Cell Rep."},{"key":"B100","doi-asserted-by":"publisher","first-page":"630502","DOI":"10.3389\/fnins.2021.630502","article-title":"APOE and Alzheimer\u2019s disease: From lipid transport to physiopathology and therapeutics.","volume":"15","author":"Husain","year":"2021","journal-title":"Front. Neurosci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2147\/CIA.S11718","article-title":"Late onset alzheimer\u2019s disease in older people.","volume":"5","author":"Isik","year":"2010","journal-title":"Clin. Interv. Aging"},{"key":"B102","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1146\/annurev-biophys-062215-010822","article-title":"CRISPR\u2013Cas9 structures and mechanisms.","volume":"46","author":"Jiang","year":"2017","journal-title":"Annu. Rev. Biophys"},{"key":"B103","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.gendis.2023.03.017","article-title":"CRISPR\/Cas9 system and its applications in nervous system diseases.","volume":"11","author":"Jiang","year":"2024","journal-title":"Genes Dis."},{"key":"B104","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA\u2013guided DNA endonuclease in adaptive bacterial immunity.","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"B105","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/978-981-96-0259-9_3","article-title":"Alzheimer\u2019s disease: Epidemiology, etiology, risk factors, and future predictions","author":"Jojo","year":"2025","journal-title":"Multi-Factorial Approach as a Therapeutic Strategy for the Management of Alzheimer\u2019s Disease"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.2217\/nnm-2022-0096","article-title":"Formulation and clinical advancement of nanourchins: A novel multibranched nanoparticulate drug-delivery system.","volume":"17","author":"Joshi","year":"2022","journal-title":"Nanomedicine"},{"key":"B107","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11481-016-9724-3","article-title":"Destination brain: The past, present, and future of therapeutic gene delivery.","volume":"12","author":"Joshi","year":"2017","journal-title":"J. Neuroimmune Pharmacol"},{"key":"B108","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41582-020-0373-z","article-title":"CRISPR-based functional genomics for neurological disease.","volume":"16","author":"Kampmann","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.biopsych.2014.05.006","article-title":"Alzheimer\u2019s disease risk genes and mechanisms of disease pathogenesis.","volume":"77","author":"Karch","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B110","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1093\/aje\/kwh018","article-title":"Relation of education and occupation-based socioeconomic status to incident Alzheimer\u2019s disease.","volume":"159","author":"Karp","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.neures.2017.10.012","article-title":"Neurexins and neuropsychiatric disorders.","volume":"127","author":"Kasem","year":"2018","journal-title":"Neurosci. Res"},{"key":"B112","doi-asserted-by":"publisher","first-page":"e51256","DOI":"10.7759\/cureus.51256","article-title":"Neurological manifestations of infectious diseases: Insights from recent cases.","volume":"15","author":"Kashyap","year":"2023","journal-title":"Cureus"},{"key":"B113","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0165-0327(93)90026-g","article-title":"Sex and depression in the National comorbidity Survey I: Lifetime prevalence, chronicity and recurrence.","volume":"29","author":"Kessler","year":"1993","journal-title":"J. Affect. Disord."},{"key":"B114","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis.","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"B115","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40035-025-00465-w","article-title":"Second-generation anti-amyloid monoclonal antibodies for Alzheimer\u2019s disease: Current landscape and future perspectives.","volume":"14","author":"Kim","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"B116","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apolipoprotein E in Alzheimer\u2019s disease.","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"B117","doi-asserted-by":"publisher","first-page":"R45","DOI":"10.1093\/hmg\/ddv253","article-title":"CNVs in neuropsychiatric disorders.","volume":"24","author":"Kirov","year":"2015","journal-title":"Hum. Mol. Genet"},{"key":"B118","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1212\/wnl.56.12.1683","article-title":"Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.","volume":"56","author":"Kivipelto","year":"2001","journal-title":"Neurology"},{"key":"B119","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1212\/wnl.45.4.741","article-title":"Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland.","volume":"45","author":"Koivisto","year":"1995","journal-title":"Neurology"},{"key":"B120","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nature17946","article-title":"Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage.","volume":"533","author":"Komor","year":"2016","journal-title":"Nature"},{"key":"B121","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1089\/nat.2018.0721","article-title":"Lipid nanoparticles enabling gene therapies: From concepts to clinical utility.","volume":"28","author":"Kulkarni","year":"2018","journal-title":"Nucleic Acid Ther."},{"key":"B122","doi-asserted-by":"publisher","first-page":"a006320","DOI":"10.1101\/cshperspect.a006320","article-title":"Animal models of Alzheimer disease.","volume":"2","author":"LaFerla","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B123","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1001\/jamainternmed.2016.6807","article-title":"A comparison of the prevalence of dementia in the United States in 2000 and 2012.","volume":"177","author":"Langa","year":"2017","journal-title":"JAMA Intern. Med."},{"key":"B124","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/519410a","article-title":"Don\u2019t edit the human germ line.","volume":"519","author":"Lanphier","year":"2015","journal-title":"Nature"},{"key":"B125","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1212\/01.wnl.0000034176.07159.f8","article-title":"Incidence and outcome of mild cognitive impairment in a population-based prospective cohort.","volume":"59","author":"Larrieu","year":"2002","journal-title":"Neurology"},{"key":"B126","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/s41551-017-0137-2","article-title":"Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair.","volume":"1","author":"Lee","year":"2017","journal-title":"Nat. Biomed. Eng."},{"key":"B127","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1186\/s12967-024-05570-4","article-title":"Harnessing the evolving CRISPR\/Cas9 for precision oncology.","volume":"22","author":"Li","year":"2024","journal-title":"J. Transl. Med"},{"key":"B128","doi-asserted-by":"publisher","first-page":"7736","DOI":"10.3390\/ijms24097736","article-title":"Viral vector-based gene therapy.","volume":"24","author":"Li","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B129","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jbiotec.2015.04.024","article-title":"Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection.","volume":"208","author":"Liang","year":"2015","journal-title":"J. Biotechnol."},{"key":"B130","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.neuron.2018.05.008.","article-title":"APOE4 causes widespread molecular and cellular alterations associated with Alzheimer\u2019s disease phenotypes in human iPSC-derived brain cell types.","volume":"98","author":"Lin","year":"2018","journal-title":"Neuron"},{"key":"B131","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jconrel.2017.09.012","article-title":"Delivery strategies of the CRISPER\/Cas9 gene-editing system for therapeutic applications.","volume":"266","author":"Liu","year":"2017","journal-title":"J. Control. Release"},{"key":"B132","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/S0140-6736(18)31129-2","article-title":"Autism spectrum disorder.","volume":"392","author":"Lord","year":"2018","journal-title":"Lancet"},{"key":"B133","doi-asserted-by":"publisher","first-page":"803894","DOI":"10.3389\/fnins.2021.803894","article-title":"Application of CRISPR\/Cas9 in Alzheimer\u2019s disease.","volume":"15","author":"Lu","year":"2021","journal-title":"Front. Neurosci"},{"key":"B134","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s12031-016-0839-z","article-title":"The complex role of apolipoprotein E in Alzheimer\u2019s disease: An overview and update.","volume":"60","author":"Mahoney-Sanchez","year":"2016","journal-title":"J. Mol. Neurosci"},{"key":"B135","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/0971-6866.112870","article-title":"Delivery systems for gene therapy.","volume":"19","author":"Mali","year":"2013","journal-title":"Indian J. Hum. Genet"},{"key":"B136","doi-asserted-by":"publisher","first-page":"20","DOI":"10.2174\/1566523222666220328142427","article-title":"Gene therapy, a potential therapeutic tool for neurological and neuropsychiatric disorders: Applications, challenges and future perspective.","volume":"23","author":"Mani","year":"2023","journal-title":"Curr. Gene Ther."},{"key":"B137","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.phrs.2019.04.026","article-title":"Neuroprotection in non-transgenic and transgenic mouse models of Alzheimer\u2019s disease by positive modulation of \u03c31 receptors.","volume":"144","author":"Maurice","year":"2019","journal-title":"Pharmacol. Res"},{"key":"B138","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1001\/jamapsychiatry.2019.3360","article-title":"Schizophrenia\u2014an overview.","volume":"77","author":"McCutcheon","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"B139","doi-asserted-by":"publisher","first-page":"895713","DOI":"10.3389\/fbioe.2022.895713","article-title":"Viral vectors for the in vivo delivery of CRISPR components: Advances and challenges.","volume":"10","author":"Mengstie","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B140","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1212\/wnl.58.2.209","article-title":"Incidence of AD may decline in the early 90s for men, later for women: The Cache County study.","volume":"58","author":"Miech","year":"2002","journal-title":"Neurology"},{"key":"B141","first-page":"14","article-title":"Sex and gender differences in Alzheimer\u2019s disease dementia.","volume":"35","author":"Mielke","year":"2018","journal-title":"Psychiatr. Times"},{"key":"B142","doi-asserted-by":"publisher","first-page":"S70","DOI":"10.1161\/CIRCOUTCOMES.115.002461","article-title":"Impaired cognition and brain atrophy decades after hypertensive pregnancy disorders.","volume":"9","author":"Mielke","year":"2016","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"B143","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2147\/CLEP.S37929","article-title":"Clinical epidemiology of Alzheimer\u2019s disease: Assessing sex and gender differences.","volume":"6","author":"Mielke","year":"2014","journal-title":"Clin. Epidemiol"},{"key":"B144","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.mrfmmm.2008.10.011","article-title":"Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases.","volume":"667","author":"Migliore","year":"2009","journal-title":"Mutat. Res."},{"key":"B145","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40478-019-0672-z","article-title":"Young adult-onset, very slowly progressive cognitive decline with spastic paraparesis in Alzheimer\u2019s disease with cotton wool plaques due to a novel presenilin1 G417S mutation.","volume":"7","author":"Miki","year":"2019","journal-title":"Acta Neuropathol. Commun"},{"key":"B146","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1089\/crispr.2019.0024","article-title":"Genetic protection modifications: Moving beyond the binary distinction between therapy and enhancement for human genome editing.","volume":"2","author":"Mikkelsen","year":"2019","journal-title":"CRISPR J."},{"key":"B147","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1002\/anie.201610209","article-title":"Non-viral CRISPR\/Cas gene editing in vitro and in vivo enabled by synthetic nanoparticle co-delivery of Cas9 mRNA and sgRNA.","volume":"129","author":"Miller","year":"2017","journal-title":"Angew. Chem."},{"key":"B148","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in early Alzheimer\u2019s disease.","volume":"384","author":"Mintun","year":"2021","journal-title":"N. Eng. J. Med."},{"key":"B149","doi-asserted-by":"publisher","first-page":"13194","DOI":"10.1074\/jbc.RA120.012904","article-title":"Amyloid precursor protein 770 is specifically expressed and released from platelets.","volume":"295","author":"Miura","year":"2020","journal-title":"J. Biol. Chem"},{"key":"B150","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41593-022-01207-1","article-title":"An RNA-targeting CRISPR\u2013Cas13d system alleviates disease-related phenotypes in Huntington\u2019s disease models.","volume":"26","author":"Morelli","year":"2023","journal-title":"Nat. Neurosci."},{"key":"B151","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13024-018-0265-5","article-title":"iPSC-derived familial Alzheimer\u2019s PSEN2 N141I cholinergic neurons exhibit mutation-dependent molecular pathology corrected by insulin signaling.","volume":"13","author":"Moreno","year":"2018","journal-title":"Mol. Neurodegen"},{"key":"B152","doi-asserted-by":"publisher","first-page":"17159","DOI":"10.1038\/s41598-024-67980-0","article-title":"An ecological study shows increased prevalence of autism spectrum disorder in children living in a heavily polluted area.","volume":"14","author":"Moschetti","year":"2024","journal-title":"Sci. Rep"},{"key":"B153","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1021\/acs.bioconjchem.7b00057","article-title":"In vivo delivery of CRISPR\/Cas9 for therapeutic gene editing: Progress and challenges.","volume":"28","author":"Mout","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"B154","doi-asserted-by":"publisher","first-page":"e2586","DOI":"10.21769\/BioProtoc.2586","article-title":"Cytosolic and nuclear delivery of CRISPR\/Cas9-ribonucleoprotein for gene editing using arginine functionalized gold nanoparticles.","volume":"7","author":"Mout","year":"2017","journal-title":"Bio Protoc"},{"key":"B155","doi-asserted-by":"publisher","first-page":"18694","DOI":"10.1074\/jbc.M801322200","article-title":"Promotion of BACE1 mRNA alternative splicing reduces amyloid \u03b2-peptide production.","volume":"283","author":"Mowrer","year":"2008","journal-title":"J. Biol. Chem"},{"key":"B156","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng0892-345","article-title":"A pathogenic mutation for probable Alzheimer\u2019s disease in the APP gene at the N\u2013terminus of \u03b2\u2013amyloid.","volume":"1","author":"Mullan","year":"1992","journal-title":"Nat. Genet."},{"key":"B157","doi-asserted-by":"publisher","first-page":"977411","DOI":"10.3389\/fnagi.2022.977411","article-title":"Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer\u2019s disease.","volume":"14","author":"Mumtaz","year":"2022","journal-title":"Front. Aging Neurosci"},{"key":"B158","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.mpmed.2020.06.002","article-title":"Stroke: Causes and clinical features.","volume":"48","author":"Murphy","year":"2020","journal-title":"Medicine"},{"key":"B159","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.3390\/cells9071608","article-title":"Latest developed strategies to minimize the off-target effects in CRISPR-Cas-mediated genome editing.","volume":"9","author":"Naeem","year":"2020","journal-title":"Cells"},{"key":"B160","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1038\/s41467-018-04238-0","article-title":"Generation of App knock-in mice reveals deletion mutations protective against Alzheimer\u2019s disease-like pathology.","volume":"9","author":"Nagata","year":"2018","journal-title":"Nat. Commun"},{"key":"B161","doi-asserted-by":"publisher","first-page":"18947","DOI":"10.1038\/s41598-019-55302-8","article-title":"Plasmid-based and-free methods using CRISPR\/Cas9 system for replacement of targeted genes in Colletotrichum sansevieriae.","volume":"9","author":"Nakamura","year":"2019","journal-title":"Sci. Rep."},{"key":"B162","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2174\/1874196702008010006","article-title":"Human brain disorders: A review.","volume":"8","author":"Naz","year":"2020","journal-title":"TOBIO J."},{"key":"B163","author":"Nesterova","year":"2019","journal-title":"Disease Pathways: An Atlas of Human Disease Signaling Pathways."},{"key":"B164","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.cell.2014.02.001","article-title":"Crystal structure of Cas9 in complex with guide RNA and target DNA.","volume":"156","author":"Nishimasu","year":"2014","journal-title":"Cell"},{"key":"B165","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.cell.2014.01.027","article-title":"Generation of gene-modified cynomolgus monkey via Cas9\/RNA-mediated gene targeting in one-cell embryos.","volume":"156","author":"Niu","year":"2014","journal-title":"Cell"},{"key":"B166","doi-asserted-by":"publisher","first-page":"567","DOI":"10.17179\/excli2023-6155","article-title":"CRISPR\/Cas9 genome editing for neurodegenerative diseases.","volume":"22","author":"Nojadeh","year":"2023","journal-title":"EXCLI J."},{"key":"B167","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/00002727-200504000-00010","article-title":"Traumatic brain injury: A review.","volume":"28","author":"Nolan","year":"2005","journal-title":"Crit. Care Nurs. Q"},{"key":"B168","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1089\/regen.2021.0016","article-title":"Prime Editing, a novel genome-editing tool that may surpass conventional CRISPER\/Cas9.","volume":"1","author":"Ochoa-Sanchez","year":"2021","journal-title":"Re:GEN Open"},{"key":"B169","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.1016\/j.jcyt.2018.02.275","article-title":"Caspase-6 knock-out using CRISPR\/Cas9 improves cognitive behavior in the 3xTg mouse model of Alzheimer\u2019s disease.","volume":"20","author":"Offen","year":"","journal-title":"Cytotherapy"},{"key":"B170","doi-asserted-by":"publisher","first-page":"S18","DOI":"10.1016\/j.jcyt.2018.02.036","article-title":"Towards gene-editing treatment for Alzheimer\u2019s disease: ApoE4 allele-specific knockout using a CRISPR cas9 variant.","volume":"20","author":"Offen","year":"","journal-title":"Cytotherapy"},{"key":"B171","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.cbpa.2015.10.001","article-title":"How specific is CRISPR\/Cas9 really?","volume":"29","author":"O\u2019Geen","year":"2015","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B172","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s40478-017-0475-z","article-title":"CRISPR\/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer\u2019s PSEN2 N141I neurons.","volume":"5","author":"Ortiz-Virumbrales","year":"2017","journal-title":"Acta Neuropathol. Commun"},{"key":"B173","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.cbpa.2015.10.001","article-title":"Past, present, and future of CRISPR genome editing technologies.","volume":"187","author":"Pacesa","year":"2024","journal-title":"Cell"},{"key":"B174","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nature17664","article-title":"Efficient introduction of specific homozygous and heterozygous mutations using CRISPR\/Cas9.","volume":"533","author":"Paquet","year":"2016","journal-title":"Nature"},{"key":"B175","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41593-019-0352-0","article-title":"In vivo neuronal gene editing via CRISPR\u2013Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer\u2019s disease.","volume":"22","author":"Park","year":"2019","journal-title":"Nat. Neurosci"},{"key":"B176","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1177\/10600280231218253","article-title":"Lecanemab: A humanized monoclonal antibody for the treatment of early alzheimer disease.","volume":"58","author":"Park","year":"2024","journal-title":"Ann. Pharmacother."},{"key":"B177","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1212\/WNL.0b013e3181f11d85","article-title":"Prevalence of mild cognitive impairment is higher in men: The mayo clinic study of aging.","volume":"75","author":"Petersen","year":"2010","journal-title":"Neurology"},{"key":"B178","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.scr.2016.08.002","article-title":"Generation of a gene-corrected isogenic control cell line from an Alzheimer\u2019s disease patient iPSC line carrying a A79V mutation in PSEN1.","volume":"17","author":"Pires","year":"2016","journal-title":"Stem Cell Res"},{"key":"B179","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1159\/000109998","article-title":"Prevalence of dementia in the United States: The aging, demographics, and memory study.","volume":"29","author":"Plassman","year":"2007","journal-title":"Neuroepidemiology"},{"key":"B180","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.scr.2016.09.018","article-title":"Generation of a gene-corrected isogenic control hiPSC line derived from a familial Alzheimer\u2019s disease patient carrying a L150P mutation in presenilin 1.","volume":"17","author":"Poon","year":"2016","journal-title":"Stem Cell Res"},{"key":"B181","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.mcn.2017.05.007","article-title":"Application of CRISPR\/Cas9 to the study of brain development and neuropsychiatric disease.","volume":"82","author":"Powell","year":"2017","journal-title":"Mol. Cell. Neurosci"},{"key":"B182","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1037\/a0012838","article-title":"Gender and education impact on brain aging: A general cognitive factor approach.","volume":"23","author":"Proust-Lima","year":"2008","journal-title":"Psychol"},{"key":"B183","doi-asserted-by":"publisher","first-page":"947","DOI":"10.3390\/cancers14040947","article-title":"Current status of CRISPR\/Cas9 application in clinical cancer research: Opportunities and challenges.","volume":"14","author":"Rafii","year":"2022","journal-title":"Cancers"},{"key":"B184","doi-asserted-by":"publisher","first-page":"9416","DOI":"10.1007\/s12035-024-04143-2","article-title":"Application of CRISPR\/Cas9 system in the treatment of Alzheimer\u2019s disease and neurodegenerative diseases.","volume":"61","author":"Rahimi","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B185","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s12035-018-1068-y","article-title":"Targeted gene editing of glia maturation factor in microglia: A novel Alzheimer\u2019s disease therapeutic target.","volume":"56","author":"Raikwar","year":"2019","journal-title":"Mol. Neurobiol"},{"key":"B186","doi-asserted-by":"publisher","first-page":"3076","DOI":"10.1093\/brain\/awv231","article-title":"GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer\u2019s disease implicates microglial activation gene IL1RAP.","volume":"138","author":"Ramanan","year":"2015","journal-title":"Brain"},{"key":"B187","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1089\/crispr.2021.0134","article-title":"Electroporation-mediated delivery of Cas9 ribonucleoproteins results in high levels of gene editing in primary hepatocytes.","volume":"5","author":"Rathbone","year":"2022","journal-title":"CRISPR J."},{"key":"B188","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1136\/jmg.2005.033456","article-title":"Molecular diagnosis of autosomal dominant early onset Alzheimer\u2019s disease: An update.","volume":"42","author":"Raux","year":"2005","journal-title":"J. Med. Genet"},{"key":"B189","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/B978-0-443-13205-6.00012-1","article-title":"Nanotechnology-based delivery for CRISPR-Cas 9 cargo in Alzheimer\u2019s disease","author":"Rawal","year":"2024","journal-title":"Alzheimer\u2019s Disease and Advanced Drug Delivery Strategies"},{"key":"B190","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.ymthe.2004.07.003","article-title":"Site-specific integration of functional transgenes into the human genome by adeno\/AAV hybrid vectors.","volume":"10","author":"Recchia","year":"2004","journal-title":"Mol. Ther"},{"key":"B191","doi-asserted-by":"publisher","first-page":"11734","DOI":"10.3390\/ijms231911734","article-title":"Experimental and clinical biomarkers for progressive evaluation of neuropathology and therapeutic interventions for acute and chronic neurological disorders.","volume":"23","author":"Reddy","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"B192","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1042\/BJ20130316","article-title":"CRISPR interference: A structural perspective.","volume":"453","author":"Reeks","year":"2013","journal-title":"Biochem. J"},{"key":"B193","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.3390\/ijms22031102","article-title":"Nanotechnology therapy for Alzheimer\u2019s disease memory impairment attenuation.","volume":"22","author":"Ribari\u010d","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"B194","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1212\/WNL.0000000000000055","article-title":"Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal.","volume":"82","author":"Roberts","year":"2014","journal-title":"Neurology"},{"key":"B195","doi-asserted-by":"publisher","first-page":"439","DOI":"10.4172\/2161-0460.1000439","article-title":"The potential of CRISPR\/Cas9 gene editing as a treatment strategy for Alzheimer\u2019s disease.","volume":"8","author":"Rohn","year":"2018","journal-title":"J. Alzheimers Dis. Park"},{"key":"B196","doi-asserted-by":"publisher","first-page":"102372","DOI":"10.1016\/j.stemcr.2024.11.002","article-title":"Optimized prime editing of the Alzheimer\u2019s disease-associated APOE4 mutation.","volume":"20","author":"Rottner","year":"2025","journal-title":"Stem Cell Rep."},{"key":"B197","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1192\/bjp.bp.112.119479","article-title":"Socioeconomic status as a risk factor for dementia death: Individual participant meta-analysis of 86 508 men and women from the UK.","volume":"203","author":"Russ","year":"2013","journal-title":"Br. J. Psychiatry"},{"key":"B198","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3389\/fnins.2019.01012","article-title":"Mutational analysis of sigma-1 receptor\u2019s role in synaptic stability.","volume":"13","author":"Ryskamp","year":"2019","journal-title":"Front. Neurosci"},{"key":"B199","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/s42003-021-02272-1","article-title":"Genome-wide CRISPR screen identifies protein pathways modulating tau protein levels in neurons.","volume":"4","author":"Sanchez","year":"2021","journal-title":"Commun. Biol."},{"key":"B200","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1038\/s41467-018-05262-w","article-title":"Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID.","volume":"9","author":"Sasaguri","year":"2018","journal-title":"Nat. Commun"},{"key":"B201","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1016\/j.stem.2024.06.001","article-title":"Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.","volume":"31","author":"Saurat","year":"2024","journal-title":"Cell Stem Cell"},{"key":"B202","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ymgme.2017.10.007","article-title":"Treatment of brain disease in the mucopolysaccharidoses.","author":"Scarpa","year":"2017","journal-title":"Mol. Genet. Metab"},{"key":"B203","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/14737175.2024.2333970","article-title":"Profiling lecanemab as a treatment option for Alzheimer\u2019s disease.","volume":"24","author":"Schiller","year":"2024","journal-title":"Expert Rev. Neurother."},{"key":"B204","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1111\/bpa.12881","article-title":"Applying gene-editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer\u2019s disease.","volume":"30","author":"Schrauben","year":"2020","journal-title":"Brain Pathol."},{"key":"B205","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/s41418-019-0409-3","article-title":"Impaired adult neurogenesis is an early event in Alzheimer\u2019s disease neurodegeneration, mediated by intracellular A\u03b2 oligomers.","volume":"27","author":"Scopa","year":"2020","journal-title":"Cell Death Differ"},{"key":"B206","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13024-020-00399-z","article-title":"Modeling the \u03b2-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer\u2019s disease.","volume":"15","author":"Serneels","year":"2020","journal-title":"Mol. Neurodegenerat"},{"key":"B207","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.ajpath.2015.10.010","article-title":"Plaque-associated local toxicity increases over the clinical course of Alzheimer disease.","volume":"186","author":"Serrano-Pozo","year":"2016","journal-title":"Am. J. Pathol"},{"key":"B208","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches.","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol."},{"key":"B209","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/ana.24369","article-title":"APOE \u03b52 is associated with milder clinical and pathological Alzheimer disease.","volume":"77","author":"Serrano-Pozo","year":"2015","journal-title":"Ann. Neurol."},{"key":"B210","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease.","volume":"303","author":"Seshadri","year":"2010","journal-title":"JAMA"},{"key":"B211","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1212\/wnl.49.6.1498","article-title":"Lifetime risk of dementia and Alzheimer\u2019s disease: The impact of mortality on risk estimates in the Framingham Study.","volume":"49","author":"Seshadri","year":"1997","journal-title":"Neurology"},{"key":"B212","doi-asserted-by":"publisher","first-page":"239","DOI":"10.18699\/vjgb-24-28","article-title":"Non-viral systems for intracellular delivery of genome editing tools.","volume":"28","author":"Shaikhutdinov","year":"2024","journal-title":"Vavilov J. Genet. Breed."},{"key":"B213","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrg3899","article-title":"High-throughput functional genomics using CRISPR\u2013Cas9.","volume":"16","author":"Shalem","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"B214","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/B978-0-443-23841-3.00014-5","article-title":"CRISPR\/Cas9 gene editing: A new hope for Alzheimer\u2019s disease","author":"Shareena","year":"2025","journal-title":"Targeted Therapy for the Central Nervous System"},{"key":"B215","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ibneur.2022.06.002","article-title":"Exploring the zinc-related transcriptional landscape in Alzheimer\u2019s disease.","volume":"13","author":"Shippy","year":"2022","journal-title":"IBRO Neurosci. Rep."},{"key":"B216","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1212\/01.wnl.0000144281.38555.e3","article-title":"Vascular risk factors, incidence of MCI, and rates of progression to dementia.","volume":"63","author":"Solfrizzi","year":"2004","journal-title":"Neurology"},{"key":"B217","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1093\/toxsci\/kfz049","article-title":"Mechanistic interplay between autophagy and apoptotic signaling in endosulfan-induced dopaminergic neurotoxicity: Relevance to the adverse outcome pathway in pesticide neurotoxicity.","volume":"169","author":"Song","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B218","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1146\/annurev-biochem-072911-172315","article-title":"CRISPR-mediated adaptive immune systems in bacteria and archaea.","volume":"82","author":"Sorek","year":"2013","journal-title":"Annu. Rev. Biochem"},{"key":"B219","doi-asserted-by":"publisher","DOI":"10.1101\/310193","article-title":"A CRISPR\/Cas9 based strategy to manipulate the Alzheimer\u2019s amyloid pathway.","author":"Sun","year":"2018","journal-title":"bioRxiv [Preprint]"},{"key":"B220","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41467-018-07971-8","article-title":"CRISPR\/Cas9 editing of APP C-terminus attenuates \u03b2-cleavage and promotes \u03b1-cleavage.","volume":"10","author":"Sun","year":"2019","journal-title":"Nat. Commun."},{"key":"B221","doi-asserted-by":"publisher","first-page":"E476","DOI":"10.1073\/pnas.1618657114","article-title":"Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of A\u03b242 and A\u03b240 peptides by \u03b3-secretase.","volume":"114","author":"Sun","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B222","doi-asserted-by":"crossref","first-page":"12197","DOI":"10.1002\/ange.201506030","article-title":"Self-assembled DNA nanoclews for the efficient delivery of CRISPR\u2013Cas9 for genome editing.","volume":"127","author":"Sun","year":"2015","journal-title":"Angew. Chem"},{"key":"B223","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood-brain barrier: From physiology to disease and back.","volume":"99","author":"Sweeney","year":"2019","journal-title":"Physiol. Rev."},{"key":"B224","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nbt.3055","article-title":"In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9.","volume":"33","author":"Swiech","year":"2015","journal-title":"Nat. Biotechnol"},{"key":"B225","doi-asserted-by":"publisher","first-page":"7333","DOI":"10.3390\/ijms25137333","article-title":"Viral and non-viral systems to deliver gene therapeutics to clinical targets.","volume":"25","author":"Taghdiri","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B226","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jconrel.2022.01.013","article-title":"Delivery of CRISPR-Cas tools for in vivo genome editing therapy: Trends and challenges.","volume":"342","author":"Taha","year":"2022","journal-title":"J. Control. Release"},{"key":"B227","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3233\/JAD-171058","article-title":"Generation of a new tau knockout (tau \u0394ex1) line using CRISPR\/Cas9 genome editing in mice.","volume":"62","author":"Tan","year":"2018","journal-title":"J. Alzheimers Dis"},{"key":"B228","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s40291-024-00738-6","article-title":"Molecular Therapeutics in Development to Treat Alzheimer\u2019s Disease.","volume":"29","author":"Tartaglia","year":"2025","journal-title":"Mol. Diagn. Ther."},{"key":"B229","doi-asserted-by":"publisher","first-page":"S421","DOI":"10.3233\/JAD-141461","article-title":"Spreading of amyloid, tau, and microvascular pathology in Alzheimer\u2019s disease: Findings from neuropathological and neuroimaging studies.","volume":"42","author":"Thal","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"B230","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1097\/MS9.0000000000001500","article-title":"Application of CRISPR\/Cas9 in the management of Alzheimer\u2019s disease and Parkinson\u2019s disease: A review.","volume":"86","author":"Thapar","year":"2024","journal-title":"Ann. Med. Surg."},{"key":"B231","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.59888\/ajosh.v3i5.500","article-title":"Ethics and intellectual property rights in genetic therapy.","volume":"3","author":"Tjandrawinata","year":"2025","journal-title":"Asian J. Soc. Hum."},{"key":"B232","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.3390\/ijms25031536","article-title":"Attention deficit hyperactivity disorder (ADHD) and polyphenols: A systematic review.","volume":"25","author":"Turiaco","year":"2024","journal-title":"Int. J. Mol. Sci"},{"key":"B233","doi-asserted-by":"publisher","first-page":"797","DOI":"10.2147\/CIA.S325026","article-title":"Role of aducanumab in the treatment of Alzheimer\u2019s disease: Challenges and opportunities.","volume":"17","author":"Vaz","year":"2022","journal-title":"Clin. Interv. Aging"},{"key":"B234","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/ana.25455","article-title":"Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in Alzheimer\u2019s disease.","volume":"85","author":"Wadhwani","year":"2019","journal-title":"Ann. Neurol"},{"key":"B235","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41591-018-0004-z","article-title":"Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector.","volume":"24","author":"Wang","year":"2018","journal-title":"Nat. Med."},{"key":"B236","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1002\/anie.201708689","article-title":"Thermo-triggered release of CRISPR-Cas9 system by lipid-encapsulated gold nanoparticles for tumor therapy.","volume":"57","author":"Wang","year":"2018","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B237","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.cell.2020.03.023","article-title":"CRISPR-based therapeutic genome editing: Strategies and in vivo delivery by AAV vectors.","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"B238","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.4049\/jimmunol.1100333","article-title":"Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis.","volume":"187","author":"Wang","year":"2011","journal-title":"J. Immunol"},{"key":"B239","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.24272\/j.issn.2095-8137.2024.274","article-title":"Animal models of Alzheimer\u2019s disease: Current strategies and new directions.","volume":"45","author":"Wang","year":"2024","journal-title":"Zool. Res."},{"key":"B240","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3978\/j.issn.2305-5839.2015.03.49","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease.","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"B241","doi-asserted-by":"publisher","first-page":"9243","DOI":"10.1021\/acsnano.0c04707","article-title":"Delivery of tissue-targeted scalpels: Opportunities and challenges for in vivo CRISPR\/Cas-based genome editing.","volume":"14","author":"Wei","year":"2020","journal-title":"ACS Nano"},{"key":"B242","doi-asserted-by":"publisher","first-page":"9455","DOI":"10.3390\/ijms24119455","article-title":"Peptide-based nanoparticles for systemic extrahepatic delivery of therapeutic nucleotides.","volume":"24","author":"Wickline","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B243","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1111\/j.1532-5415.1993.tb06738.x","article-title":"Effects of age, gender and education on selected neuropsychological tests in an elderly community cohort.","volume":"41","author":"Wiederholt","year":"1993","journal-title":"J. Am. Geriatr. Soc."},{"key":"B244","doi-asserted-by":"publisher","first-page":"6385","DOI":"10.1073\/pnas.1820160116","article-title":"GSAP modulates gamma-secretase specificity by inducing conformational change in PS1.","volume":"116","author":"Wong","year":"2019","journal-title":"Proc. Natl Acad. Sci. U. S. A"},{"key":"B245","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cell.2015.12.035","article-title":"Biology and applications of CRISPR systems: Harnessing nature\u2019s toolbox for genome engineering.","volume":"164","author":"Wright","year":"2016","journal-title":"Cell"},{"key":"B246","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3233\/JAD-2011-102031","article-title":"Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer\u2019s disease.","volume":"25","author":"Wu","year":"2011","journal-title":"J. Alzheimers Dis"},{"key":"B247","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.neuron.2015.02.010","article-title":"Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer\u2019s disease.","volume":"85","author":"Xia","year":"2015","journal-title":"Neuron"},{"key":"B248","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/v11010028","article-title":"Viral delivery systems for CRISPR.","volume":"11","author":"Xu","year":"2019","journal-title":"Viruses"},{"key":"B249","doi-asserted-by":"publisher","first-page":"16026","DOI":"10.1038\/celldisc.2016.26","article-title":"Alzheimer\u2019s disease-associated mutations increase amyloid precursor protein resistance to \u03b3-secretase cleavage and the A\u03b242\/A\u03b240 ratio.","volume":"2","author":"Xu","year":"2016","journal-title":"Cell Discov"},{"key":"B250","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41422-019-0142-y","article-title":"CRISPR\/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys.","volume":"29","author":"Yang","year":"2019","journal-title":"Cell Res"},{"key":"B251","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1159\/000081072","article-title":"Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice.","volume":"73","author":"Yu","year":"2005","journal-title":"Pharmacology"},{"key":"B252","first-page":"333","article-title":"The global economic impact of neurodegenerative diseases: Opportunities and challenges","author":"Zahra","year":"2020","journal-title":"Bioeconomy for Sustainable Development"},{"key":"B253","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14740338.2025.2467180","article-title":"Safety issues of donepezil combined with memantine in Alzheimer\u2019s disease population: Real-world pharmacovigilance.","volume":"24","author":"Zeng","year":"2025","journal-title":"Expert Opin. Drug Saf."},{"key":"B254","doi-asserted-by":"publisher","first-page":"236","DOI":"10.54254\/2753-8818\/33\/20240896","article-title":"Research progress and future development direction of Alzheimer\u2019s therapy.","volume":"33","author":"Zhai","year":"2024","journal-title":"Theor. Nat. Sci."},{"key":"B255","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/celc.201600638","article-title":"Mesoporous NiCo2O4 micro\/nanospheres with hierarchical structures for supercapacitors and methanol electro\u2013oxidation.","volume":"4","author":"Zhang","year":"2017","journal-title":"ChemElectroChem"},{"key":"B256","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.neubiorev.2015.07.003","article-title":"Association between variant amyloid deposits and motor deficits in FAD-associated presenilin-1 mutations: A systematic review.","volume":"56","author":"Zhang","year":"2015","journal-title":"Neurosci. Biobehav. Rev"},{"key":"B257","doi-asserted-by":"publisher","first-page":"63","DOI":"10.54254\/2753-8818\/54\/2024AU0120","article-title":"Application of CRISPR\/Cas9 gene-editing technology in Alzheimer\u2019s disease.","volume":"54","author":"Zhang","year":"2024","journal-title":"Theor. Nat. Sci."},{"key":"B258","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fnmol.2020.00137","article-title":"Targeting amyloidogenic processing of APP in Alzheimer\u2019s disease.","volume":"13","author":"Zhao","year":"2020","journal-title":"Front. Mol. Neurosci"},{"key":"B259","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.neurobiolaging.2020.02.020","article-title":"Suvorexant ameliorates cognitive impairments and pathology in APP\/PS1 transgenic mice.","volume":"91","author":"Zhou","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"B260","doi-asserted-by":"publisher","first-page":"eabc7031","DOI":"10.1126\/sciadv.abc7031","article-title":"Blood-brain barrier\u2013penetrating siRNA nanomedicine for Alzheimer\u2019s disease therapy.","volume":"6","author":"Zhou","year":"2020","journal-title":"Sci. Adv."},{"key":"B261","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1089\/hum.2017.255","article-title":"Seamless genetic conversion of SMN2 to SMN1 via CRISPR\/Cpf1 and single-stranded oligodeoxynucleotides in spinal muscular atrophy patient-specific induced pluripotent stem cells.","volume":"29","author":"Zhou","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"B262","doi-asserted-by":"publisher","first-page":"7391","DOI":"10.1038\/ncomms8391","article-title":"Somatic CRISPR\/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.","volume":"6","author":"Zuckermann","year":"2015","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1578138\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T01:32:41Z","timestamp":1743989561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1578138\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":262,"alternative-id":["10.3389\/fncel.2025.1578138"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2025.1578138","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]},"article-number":"1578138"}}