{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:57:37Z","timestamp":1790949457309,"version":"4.1.0"},"reference-count":78,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss??ti?","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["362227"],"award-info":[{"award-number":["362227"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Excellence Strategy of Heidelberg University"},{"name":"Taconic Biosciences"},{"name":"Marsilius-Kolleg, Heidelberg University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Developing effective therapeutic approaches for tau-associated neurodegenerative diseases, including frontotemporal dementia and Alzheimer\u2019s disease, remains extremely challenging due to their complex pathogeneses. Membrane proteins constitute a large proportion of current therapeutic and drug delivery targets because of their key roles in essential cellular processes. Here, we examined alterations in membrane protein abundances in the prefrontal cortex of male and female mouse models of human tauopathy, JNPL3 mice, compared with sex-matched wild-type (WT) mice using quantitative proteomics. The data-independent acquisition (DIA) proteomics analysis revealed various alterations in membrane proteins involved in different altered pathways in male JNPL3 mice (e.g., nucleotide metabolism and translation) and female JNPL3 mice (e.g., mitochondrial function). In addition, we found sex-associated changes in the abundances of several proteins previously reported to be involved in tau pathology, such as Reelin, DARPP-32, Zyxin, Tbce, and Gng5, in JNPL3 mice. Our multiple-reaction monitoring absolute quantitative analysis of transporter proteins revealed reduced abundance of the main drug efflux transporter ABCB1 in male JNPL3 mice compared with WT animals, with no changes in female groups. All in all, we provide novel information on membrane proteomic changes in male and female mouse models of human tauopathy, JNPL3 mice, which could aid in developing treatments for tau-associated neurodegenerative diseases and facilitate the prediction of neuropharmacokinetics in female and male patients.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00679","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:01:54Z","timestamp":1789560114000},"page":"5599-5610","source":"Crossref","is-referenced-by-count":0,"title":["Altered Membrane\nProtein Abundance in the Cerebral\nCortex of the JNPL3 Mouse Model of Tauopathy"],"prefix":"10.1021","volume":"25","author":[{"given":"Sabrina","family":"Petralla","sequence":"first","affiliation":[{"name":"Ruprecht-Karls-University , , ,","place":["Heidelberg, Germany, DE-69120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5564-2846","authenticated-orcid":true,"given":"Jooseppi","family":"Hyva\u0308rinen","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Gynther","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Afonin","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Auriola","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Panayotova","sequence":"additional","affiliation":[{"name":"Ruprecht-Karls-University , , ,","place":["Heidelberg, Germany, DE-69120"]},{"name":"Heidelberg University , , ,","place":["Heidelberg, Germany, DE-69120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-8589","authenticated-orcid":true,"given":"Katja M.","family":"Kanninen","sequence":"additional","affiliation":[{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-961X","authenticated-orcid":true,"given":"Gert","family":"Fricker","sequence":"additional","affiliation":[{"name":"Ruprecht-Karls-University , , ,","place":["Heidelberg, Germany, DE-69120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-389X","authenticated-orcid":true,"given":"Elena","family":"Puris","sequence":"additional","affiliation":[{"name":"Ruprecht-Karls-University , , ,","place":["Heidelberg, Germany, DE-69120"]},{"name":"University of Eastern Finland , , ,","place":["Kuopio, Finland, FI-70211"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"12","key":"2026100208413774400_cit1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI168553","article-title":"Tau Pathology in\nNeurodegenerative Disease: Disease Mechanisms and Therapeutic Avenues","volume":"133","author":"Samudra","year":"2023","journal-title":"J. Clin. Invest."},{"issue":"1","key":"2026100208413774400_cit2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00533-z","article-title":"Tauopathies:\nNew Perspectives and Challenges","volume":"17","author":"Zhang","year":"2022","journal-title":"Mol. Neurodegener."},{"issue":"9","key":"2026100208413774400_cit3","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.neurol.2018.07.001","article-title":"New Classification of Tauopathies","volume":"174","author":"Ho\u0308glinger","year":"2018","journal-title":"Rev. Neurol."},{"key":"2026100208413774400_cit4","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.1016\/j.parkreldis.2015.09.020","article-title":"Tauopathies\nas Clinicopathological Entities","volume":"22","author":"Irwin","year":"2016","journal-title":"Parkinsonism\nRelat. Disord."},{"key":"2026100208413774400_cit5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-3-030-51140-1_12","article-title":"Tau\nProtein and Frontotemporal\nDementias","volume-title":"Frontotemporal Dementias","author":"Goedert","year":"2021"},{"issue":"6","key":"2026100208413774400_cit6","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.1007\/s00415-024-12314-3","article-title":"Genetic Forms of Tauopathies:\nInherited\nCauses and Implications of Alzheimer\u2019s Disease-like TAU Pathology\nin Primary and Secondary Tauopathies","volume":"271","author":"Langerscheidt","year":"2024","journal-title":"J. Neurol."},{"key":"2026100208413774400_cit7","doi-asserted-by":"publisher","DOI":"10.1038\/srep24756","article-title":"Human Wild-Type Full-Length Tau Accumulation Disrupts\nMitochondrial Dynamics and the Functions via Increasing Mitofusins","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"issue":"3","key":"2026100208413774400_cit8","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.neuron.2011.04.009","article-title":"The Many Faces of Tau","volume":"70","author":"Morris","year":"2011","journal-title":"Neuron"},{"issue":"12","key":"2026100208413774400_cit9","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1097\/00001756-199708180-00029","article-title":"Somatodendritic\nLocalization\nof Phosphorylated Tau in Neonatal and Adult Rat Cerebral Cortex","volume":"8","author":"Tashiro","year":"1997","journal-title":"NeuroReport"},{"issue":"3","key":"2026100208413774400_cit10","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00401-023-02604-x","article-title":"Cell-Specific MAPT Gene Expression\nIs Preserved in Neuronal and Glial Tau Cytopathologies in Progressive\nSupranuclear Palsy","volume":"146","author":"Forrest","year":"2023","journal-title":"Acta Neuropathol."},{"issue":"4837","key":"2026100208413774400_cit11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1126\/science.3122323","article-title":"The Primary Structure and Heterogeneity\nof Tau Protein from Mouse Brain","volume":"239","author":"Lee","year":"1988","journal-title":"Science"},{"issue":"11","key":"2026100208413774400_cit12","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41580-024-00753-9","article-title":"Cellular and Pathological\nFunctions of Tau","volume":"25","author":"Parra Bravo","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"5","key":"2026100208413774400_cit13","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1073\/pnas.72.5.1858","article-title":"A Protein\nFactor Essential for Microtubule Assembly","volume":"72","author":"Weingarten","year":"1975","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"issue":"1","key":"2026100208413774400_cit14","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative\nTauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"issue":"6","key":"2026100208413774400_cit15","doi-asserted-by":"publisher","first-page":"4566","DOI":"10.1074\/jbc.M110.199976","article-title":"Nuclear Tau, a Key\nPlayer in Neuronal DNA Protection","volume":"286","author":"Sultan","year":"2011","journal-title":"J. Biol.\nChem."},{"issue":"10","key":"2026100208413774400_cit16","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/j.jalz.2015.12.014","article-title":"Molecular Mechanism\nof Prion-like Tau-induced Neurodegeneration","volume":"12","author":"Alonso","year":"2016","journal-title":"Alzheimer\u2019s Dementia"},{"key":"2026100208413774400_cit17","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00113","article-title":"The Role of Extracellular Tau in\nthe Spreading of Neurofibrillary\nPathology","volume":"8","author":"Medina","year":"2014","journal-title":"Front. Cell. Neurosci."},{"issue":"24","key":"2026100208413774400_cit18","doi-asserted-by":"publisher","first-page":"14893","DOI":"10.1074\/jbc.M115.652693","article-title":"Tau Trimers\nAre the Minimal Propagation Unit Spontaneously Internalized to Seed\nIntracellular Aggregation","volume":"290","author":"Mirbaha","year":"2015","journal-title":"J. Biol. 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Cell Dev.\nBiol."},{"issue":"16","key":"2026100208413774400_cit22","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1007\/s00018-012-1201-4","article-title":"Membrane\nTrafficking in Neuronal Maintenance and Degeneration","volume":"70","author":"Wang","year":"2013","journal-title":"Cell Mol. Life Sci."},{"issue":"16","key":"2026100208413774400_cit23","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1212\/WNL.0b013e318250d8bc","article-title":"Blood-Brain\nBarrier: Recent Developments and Clinical Correlations","volume":"78","author":"Benarroch","year":"2012","journal-title":"Neurology"},{"issue":"8","key":"2026100208413774400_cit24","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrd4626","article-title":"SLC Transporters\nas Therapeutic Targets: Emerging Opportunities","volume":"14","author":"Lin","year":"2015","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026100208413774400_cit25","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1365051","article-title":"Sex-Specific Changes\nin Protein Expression of Membrane\nTransporters in the Brain Cortex of 5xFAD Mouse Model of Alzheimer\u2019s\nDisease","volume":"15","author":"Puris","year":"2024","journal-title":"Front. Pharmacol."},{"key":"2026100208413774400_cit26","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105741","article-title":"Altered Protein\nExpression of Membrane\nTransporters in Isolated Cerebral Microvessels and Brain Cortex of\na Rat Alzheimer\u2019s Disease Model","volume":"169","author":"Puris","year":"2022","journal-title":"Neurobiol.\nDis."},{"issue":"13","key":"2026100208413774400_cit27","doi-asserted-by":"publisher","first-page":"4771","DOI":"10.1523\/JNEUROSCI.5923-10.2011","article-title":"Common and Distinct\nMechanisms of Cognitive Flexibility in Prefrontal Cortex","volume":"31","author":"Kim","year":"2011","journal-title":"J. Neurosci."},{"issue":"3","key":"2026100208413774400_cit28","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.neures.2005.11.009","article-title":"Increased\nLevels of Granular Tau Oligomers: An Early\nSign of Brain Aging and Alzheimer\u2019s Disease","volume":"54","author":"Maeda","year":"2006","journal-title":"Neurosci. Res."},{"issue":"4","key":"2026100208413774400_cit29","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/78078","article-title":"Neurofibrillary\nTangles, Amyotrophy and Progressive Motor Disturbance in Mice Expressing\nMutant (P301L) Tau Protein","volume":"25","author":"Lewis","year":"2000","journal-title":"Nat. Genet."},{"key":"2026100208413774400_cit30","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.912995","article-title":"Mouse Models of Alzheimer\u2019s\nDisease","volume":"15","author":"Yokoyama","year":"2022","journal-title":"Front. Mol. Neurosci."},{"issue":"1","key":"2026100208413774400_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.896","article-title":"Longitudinal Evaluation\nof Tau-P301L Transgenic Mice Reveals No Cognitive Impairments at 17\nMonths of Age","volume":"8","author":"Kent","year":"2018","journal-title":"Brain Behav."},{"issue":"34","key":"2026100208413774400_cit32","doi-asserted-by":"publisher","first-page":"9115","DOI":"10.1523\/JNEUROSCI.2361-07.2007","article-title":"Immunotherapy\nTargeting Pathological Tau Conformers in a Tangle Mouse Model Reduces\nBrain Pathology with Associated Functional Improvements","volume":"27","author":"Asuni","year":"2007","journal-title":"J. Neurosci."},{"issue":"1","key":"2026100208413774400_cit33","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-34","article-title":"Tau Pathology Induces\nLoss of GABAergic Interneurons Leading to Altered Synaptic Plasticity\nand Behavioral Impairments","volume":"1","author":"Levenga","year":"2013","journal-title":"Acta Neuropathol.\nCommun."},{"issue":"5","key":"2026100208413774400_cit34","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1124\/mol.104.007443","article-title":"Isoflurane Induces a Protein Kinase C \u03b1-Dependent Increase\nin Cell-Surface Protein Level and Activity of Glutamate Transporter\nType 3","volume":"67","author":"Huang","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"2026100208413774400_cit35","doi-asserted-by":"crossref","unstructured":"Beitchman, J. A.; Krishna, G.; Bromberg, C. E.; Thomas, T. C.\n          Effects of\nIsoflurane and Urethane Anesthetics on Glutamate Neurotransmission\nin Rat Brain Using in Vivo Amperometry\n          bioRxiv\n          2023\n          10.1101\/2023.02.16.528856.","DOI":"10.1101\/2023.02.16.528856"},{"issue":"1","key":"2026100208413774400_cit36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/cm.21776","article-title":"Tau ADNP,\nand Sex","volume":"81","author":"Gozes","year":"2024","journal-title":"Cytoskeleton"},{"issue":"9","key":"2026100208413774400_cit37","doi-asserted-by":"publisher","first-page":"6383","DOI":"10.1007\/s12035-024-03990-3","article-title":"Increased Expression of Transferrin\nReceptor 1 in the Brain Cortex of 5xFAD Mouse Model of Alzheimer\u2019s\nDisease Is Associated with Activation of HIF-1 Signaling Pathway","volume":"61","author":"Petralla","year":"2024","journal-title":"Mol. Neurobiol."},{"issue":"7","key":"2026100208413774400_cit38","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.tibtech.2018.12.002","article-title":"The Ultimate qPCR Experiment:\nProducing Publication\nQuality, Reproducible Data the First Time","volume":"37","author":"Taylor","year":"2019","journal-title":"Trends\nBiotechnol."},{"issue":"1","key":"2026100208413774400_cit39","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: Neural\nNetworks and Interference Correction Enable Deep Proteome Coverage\nin High Throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"issue":"D1","key":"2026100208413774400_cit40","doi-asserted-by":"publisher","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledge\nbase in 2023","volume":"51","author":"Bateman","year":"2023","journal-title":"Nucleic Acids Res."},{"issue":"9","key":"2026100208413774400_cit41","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1021\/acs.jproteome.2c00145","article-title":"Protein Contaminants Matter: Building\nUniversal Protein Contaminant Libraries for DDA and DIA Proteomics","volume":"21","author":"Frankenfield","year":"2022","journal-title":"J. Proteome Res."},{"key":"2026100208413774400_cit42","doi-asserted-by":"crossref","unstructured":"Kistner, F.; Grossmann, J. L.; Sinn, L. R.; Demichev, V.\n          QuantUMS: Uncertainty\nMinimisation Enables Confident Quantification in Proteomics\n          BioRxiv\n          2023\n          10.1101\/2023.06.20.545604.","DOI":"10.1101\/2023.06.20.545604"},{"issue":"43","key":"2026100208413774400_cit43","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686","article-title":"Welcome to\nthe Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"JOSS"},{"issue":"7","key":"2026100208413774400_cit44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential\nExpression Analyses for RNA-Sequencing\nand Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"2026100208413774400_cit45","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling\nThe False Discovery Rate - A Practical\nAnd Powerful Approach To Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J.\nR. Stat. Soc. Series B Stat. Methodol."},{"issue":"2","key":"2026100208413774400_cit46","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1214\/16-AOAS920","article-title":"Robust Hyperparameter\nEstimation Protects against Hypervariable Genes and Improves Power\nto Detect Differential Expression","volume":"10","author":"Phipson","year":"2016","journal-title":"Ann. Appl.\nStat."},{"issue":"11","key":"2026100208413774400_cit47","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/j.ajpath.2025.05.020","article-title":"Updates\non Tau-Related Drug Targets\nand Potential Disease-Modifying Therapies for Alzheimer Disease","volume":"195","author":"Djurovic-Topalovic","year":"2025","journal-title":"Am. J. Pathol."},{"issue":"2","key":"2026100208413774400_cit48","doi-asserted-by":"publisher","first-page":"390","DOI":"10.14336\/AD.2019.0519","article-title":"Alteration in the Function and Expression\nof SLC and ABC Transporters\nin the Neurovascular Unit in Alzheimer\u2019s Disease and the Clinical\nSignificance","volume":"11","author":"Jia","year":"2020","journal-title":"Aging Dis."},{"issue":"2","key":"2026100208413774400_cit49","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3233\/JAD-170639","article-title":"ABC Transporters Are\nKey Players in Alzheimer\u2019s\nDisease","volume":"61","author":"Pereira","year":"2017","journal-title":"JAD"},{"issue":"7","key":"2026100208413774400_cit50","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16070948","article-title":"Low-Density\nLipoprotein Receptor-Related Protein 1 as a Potential Therapeutic\nTarget in Alzheimer\u2019s Disease","volume":"16","author":"Petralla","year":"2024","journal-title":"Pharmaceutics"},{"issue":"04","key":"2026100208413774400_cit51","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1055\/s-0041-1735541","article-title":"The Function and Expression of ATP-Binding Cassette\nTransporters Proteins in the Alzheimer\u2019s Disease","volume":"08","author":"Aykac","year":"2021","journal-title":"Global Med. Genet."},{"key":"2026100208413774400_cit52","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00045","article-title":"The Role of ABCB1 and\nABCA1 in Beta-Amyloid Clearance\nat the Neurovascular Unit in Alzheimer\u2019s Disease","volume":"4","author":"ElAli","year":"2013","journal-title":"Front. Physiol."},{"issue":"1","key":"2026100208413774400_cit53","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/bdd.2331","article-title":"The Role of\nthe Efflux Transporter,\nP-glycoprotein, at the Blood\u2013Brain Barrier in Drug Discovery","volume":"44","author":"Cox","year":"2023","journal-title":"Biopharm. Drug Dispos."},{"issue":"1","key":"2026100208413774400_cit54","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7905486","article-title":"P-glycoprotein (ABCB1)\nand Oxidative Stress: Focus on Alzheimer\u2019s Disease","volume":"2017","author":"Sita","year":"2017","journal-title":"Oxid. Med. Cell. 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