{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:50:44Z","timestamp":1791571844551,"version":"4.3.4"},"reference-count":118,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging of the National Institutes of Health","award":["1R03AG072110-01A1"],"award-info":[{"award-number":["1R03AG072110-01A1"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1R03AG070579-01"],"award-info":[{"award-number":["1R03AG070579-01"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1RF1AG069121"],"award-info":[{"award-number":["1RF1AG069121"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1R01AG073474"],"award-info":[{"award-number":["1R01AG073474"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1R03AG072110-01A1"],"award-info":[{"award-number":["1R03AG072110-01A1"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1R03AG070579-01"],"award-info":[{"award-number":["1R03AG070579-01"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1RF1AG069121"],"award-info":[{"award-number":["1RF1AG069121"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["1R01AG073474"],"award-info":[{"award-number":["1R01AG073474"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Anti-amyloid therapies (AATs) are increasingly being recognized as promising treatment options for Alzheimer\u2019s disease (AD). Amyloid-related imaging abnormalities (ARIAs), small areas of edema and microbleeds in the brain presenting as abnormal signals in MRIs of the brain for patients with AD, are the most common side effects of AATs. While most ARIAs are asymptomatic, they can be associated with symptoms like nausea, headache, confusion, and gait instability and, less commonly, with more serious complications such as seizures and death. Cerebral amyloid angiopathy (CAA) has been found to be a major risk for ARIA development. The identification of sensitive and reliable non-invasive biomarkers for CAA has been an area of AD research over the years, but with the approval of AATs, this area has taken on a new urgency. This comprehensive review highlights several potential biomarkers, such as A\u03b240, A\u03b240\/42, phosphorylated-tau217, neurofilament light chain, glial fibrillary acidic protein, secreted phosphoprotein 1, placental growth factor, triggering receptor expressed on myeloid cells 2, cluster of differentiation 163, proteomics, and microRNA. Identifying and staging CAA even before its consequences can be detected via neuroimaging are critical to allow clinicians to judiciously select appropriate candidates for AATs, stratify monitoring, properly manage therapeutic regimens for those experiencing symptomatic ARIAs, and optimize the treatment to achieve the best outcomes. Future studies can test potential plasma biomarkers in human beings and evaluate predictive values of individual markers for CAA severity.<\/jats:p>","DOI":"10.3390\/jcm14041070","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T03:39:47Z","timestamp":1739158787000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Plasma Biomarkers for Cerebral Amyloid Angiopathy and Implications for Amyloid-Related Imaging Abnormalities: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-1782","authenticated-orcid":false,"given":"Mo-Kyung","family":"Sin","sequence":"first","affiliation":[{"name":"College of Nursing, Seattle University, Seattle, WA 98122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Dage","sequence":"additional","affiliation":[{"name":"School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangsik","family":"Nho","sequence":"additional","affiliation":[{"name":"School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-7299","authenticated-orcid":false,"given":"N. Maritza","family":"Dowling","sequence":"additional","affiliation":[{"name":"School of Nursing, George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-624X","authenticated-orcid":false,"given":"Nicholas T.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"School of Medicine, Rush University, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan I.","family":"Levey","sequence":"additional","affiliation":[{"name":"School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6832-6424","authenticated-orcid":false,"given":"Ali","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center, Washington, DC 20422, USA"},{"name":"Department of Medicine, George Washington University, Washington, DC 20037, USA"},{"name":"Department of Medicine, Georgetown University, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2025, January 28). Alzheimer\u2019s Facts and Figures Report. Available online: https:\/\/www.alz.org\/alzheimers-dementia\/facts-figures."},{"key":"ref_2","unstructured":"National Institute on Aging (2025, January 28). Alzheimer\u2019s Disease Fact Sheet, Available online: https:\/\/www.nia.nih.gov\/health\/alzheimers-and-dementia\/alzheimers-disease-fact-sheet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","article-title":"A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer\u2019s disease with lecanemab, an anti-A\u03b2 protofibril antibody","volume":"13","author":"Swanson","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Withington, C.G., and Turner, R.S. (2022). Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer\u2019s Disease. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.862369"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.biopsych.2017.08.010","article-title":"Anti-Amyloid-\u03b2 Monoclonal Antibodies for Alzheimer\u2019s Disease: Pitfalls and Promise","volume":"83","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_6","first-page":"e688","article-title":"Validation of Plasma Amyloid-\u03b2 42\/40 for Detecting Alzheimer Disease Amyloid Plaques","volume":"98","author":"Li","year":"2022","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13195-022-01117-1","article-title":"The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer\u2019s disease: A literature review","volume":"14","author":"Brand","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1002\/acn3.635","article-title":"Aging and APOE-\u03b54 are determinative factors of plasma A\u03b242 levels","volume":"5","author":"Nakamura","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jalz.2019.04.001","article-title":"Duration of preclinical, prodromal, and dementia stages of Alzheimer\u2019s disease in relation to age, sex, and APOE genotype","volume":"15","author":"Vermunt","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_10","first-page":"e12377","article-title":"ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer\u2019s disease","volume":"9","author":"Honig","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","article-title":"Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients with Early Alzheimer Disease","volume":"79","author":"Salloway","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Doran, S.J., and Sawyer, R.P. (2024). Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1326784"},{"key":"ref_13","first-page":"255","article-title":"Clinical Development of Aducanumab, an Anti-A\u03b2 Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer\u2019s Disease","volume":"4","author":"Chiao","year":"2017","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_14","first-page":"75","article-title":"Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer\u2019s disease","volume":"2","author":"Carlson","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1889","DOI":"10.1212\/WNL.0000000000005550","article-title":"ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease","volume":"90","author":"Cummings","year":"2018","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1312889","article-title":"Phase 3 trials of solanezumab for mild-to-moderate Alzheimer\u2019s disease","volume":"370","author":"Doody","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41582-019-0281-2","article-title":"Cerebral amyloid angiopathy and Alzheimer disease\u2014One peptide, two pathways","volume":"16","author":"Greenberg","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","first-page":"393","article-title":"Ponezumab in mild-to-moderate Alzheimer\u2019s disease: Randomized phase II PET-PIB study","volume":"3","author":"Landen","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/acn3.761","article-title":"Immunotherapy with ponezumab for probable cerebral amyloid angiopathy","volume":"6","author":"Leurent","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in Early Alzheimer\u2019s Disease","volume":"384","author":"Mintun","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.14283\/jpad.2022.21","article-title":"Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer\u2019s Disease Treated with Anti-Amyloid Beta Therapy","volume":"9","author":"Barakos","year":"2022","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1212\/WNL.0000000000013053","article-title":"Decisions With Patients and Families Regarding Aducanumab in Alzheimer Disease, With Recommendations for Consent: AAN Position Statement","volume":"98","author":"Chiong","year":"2022","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11910-021-01125-y","article-title":"Critical Appraisal of Amyloid Lowering Agents in AD","volume":"21","author":"Decourt","year":"2021","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/STROKEAHA.121.036873","article-title":"Vessels Sing Their ARIAs: The Role of Vascular Amyloid in the Age of Aducanumab","volume":"53","author":"Sveikata","year":"2022","journal-title":"Stroke"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.neurobiolaging.2020.09.022","article-title":"Neuronal insulin signaling and brain structure in nondemented older adults: The Atherosclerosis Risk in Communities Study","volume":"97","author":"Walker","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_26","unstructured":"Eli Lilly and Company (2025, January 28). Lilly\u2019s Donanemab Significantly Slowed Cognitive and Functional Decline in Phase 3 Study of Early Alzheimer\u2019s Disease. Available online: https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-donanemab-significantly-slowed-cognitive-and-functional."},{"key":"ref_27","unstructured":"(2025, January 28). Highlights of Prescribing Information. Available online: https:\/\/us.eisai.com\/-\/media\/files\/useisai\/792710051-2021-08-11."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S1474-4422(22)00208-3","article-title":"The Boston criteria version 2.0 for cerebral amyloid angiopathy: A multicentre, retrospective, MRI-neuropathology diagnostic accuracy study","volume":"21","author":"Charidimou","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1212\/WNL.56.4.537","article-title":"Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston criteria","volume":"56","author":"Knudsen","year":"2001","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ana.21694","article-title":"Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy","volume":"66","author":"Verbeek","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e230009","DOI":"10.1148\/rg.230009","article-title":"Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-\u03b2 Therapy","volume":"43","author":"Agarwal","year":"2023","journal-title":"RadioGraphics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/STROKEAHA.117.016990","article-title":"Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria","volume":"49","author":"Greenberg","year":"2018","journal-title":"Stroke"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/ana.26610","article-title":"Decreased Cerebrospinal Fluid Amyloid \u03b2 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy","volume":"93","author":"Kuiperij","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1136\/jnnp-2016-314697","article-title":"The increasing impact of cerebral amyloid angiopathy: Essential new insights for clinical practice","volume":"88","author":"Banerjee","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/alz.12697","article-title":"Comparative analytical performance of multiple plasma A\u03b242 and A\u03b240 assays and their ability to predict positron emission tomography amyloid positivity","volume":"19","author":"Zicha","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhu, X., Xu, F., Hoos, M.D., Lee, H., Benveniste, H., and Nostrand, W.E.V. (2020). Reduced Levels of Cerebrospinal Fluid\/Plasma A\u03b240 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010303"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/alzrt230","article-title":"Adjusting the compass: New insights into the role of angiogenesis in Alzheimer\u2019s disease","volume":"5","author":"Jefferies","year":"2013","journal-title":"Alzheimers Res. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sheikh, A.M., Yano, S., Tabassum, S., Mitaki, S., Michikawa, M., and Nagai, A. (2023). Alzheimer\u2019s Amyloid \u03b2 Peptide Induces Angiogenesis in an Alzheimer\u2019s Disease Model Mouse through Placental Growth Factor and Angiopoietin 2 Expressions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054510"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2217\/fnl.12.6","article-title":"Clearance of amyloid-\u03b2 peptides by microglia and macrophages: The issue of what, when and where","volume":"7","author":"Lai","year":"2012","journal-title":"Future Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/jnc.12202","article-title":"Alzheimer\u2019s A\u03b242 and A\u03b240 peptides form interlaced amyloid fibrils","volume":"126","author":"Gu","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2174\/156652407782564462","article-title":"Molecular and cellular mechanisms for Alzheimer\u2019s disease: Understanding APP metabolism","volume":"7","author":"Zhang","year":"2007","journal-title":"Curr. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1750-1326-6-86","article-title":"Resorufin analogs preferentially bind cerebrovascular amyloid: Potential use as imaging ligands for cerebral amyloid angiopathy","volume":"6","author":"Han","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/psc.2789","article-title":"A\u03b242 and A\u03b240: Similarities and differences","volume":"21","author":"Qiu","year":"2015","journal-title":"J. Pept. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1074\/jbc.270.13.7013","article-title":"Amyloid beta protein (A beta) in Alzheimer\u2019s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43)","volume":"270","author":"Gravina","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40478-017-0477-x","article-title":"Distinct deposition of amyloid-\u03b2 species in brains with Alzheimer\u2019s disease pathology visualized with MALDI imaging mass spectrometry","volume":"5","author":"Kakuda","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1006\/abbi.1993.1112","article-title":"Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer\u2019s disease","volume":"301","author":"Miller","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.jacc.2017.07.724","article-title":"Cerebral Amyloid Angiopathy: Diagnosis, Clinical Implications, and Management Strategies in Atrial Fibrillation","volume":"70","author":"DeSimone","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/nprot.2006.277","article-title":"Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain","volume":"1","author":"Wilcock","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103383","DOI":"10.1016\/j.nicl.2023.103383","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative The association between white matter hyperintensities and amyloid and tau deposition","volume":"38","author":"Alban","year":"2023","journal-title":"NeuroImage Clin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1093\/brain\/awz162","article-title":"White matter hyperintensities: Relationship to amyloid and tau burden","volume":"142","author":"Knopman","year":"2019","journal-title":"Brain J. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1212\/01.WNL.0000142966.22886.20","article-title":"White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage","volume":"63","author":"Smith","year":"2004","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1212\/WNL.0000000000000732","article-title":"Posterior white matter disease distribution as a predictor of amyloid angiopathy","volume":"83","author":"Thanprasertsuk","year":"2014","journal-title":"Neurology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neurobiolaging.2020.03.008","article-title":"ADNI Investigators CSF amyloid is a consistent predictor of white matter hyperintensities across the disease course from aging to Alzheimer\u2019s disease","volume":"91","author":"Walsh","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1809","DOI":"10.1212\/WNL.0000000000012778","article-title":"Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study","volume":"97","author":"Antolini","year":"2021","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3233\/JAD-215208","article-title":"Cerebrospinal Fluid Profile of Tau, Phosphorylated Tau, A\u03b242, and A\u03b240 in Probable Cerebral Amyloid Angiopathy","volume":"87","author":"Grangeon","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Margraf, N.G., Jensen-Kondering, U., Weiler, C., Leypoldt, F., Maetzler, W., Philippen, S., Bartsch, T., Fl\u00fch, C., R\u00f6cken, C., and M\u00f6ller, B. (2022). Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.783996"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"fcad159","DOI":"10.1093\/braincomms\/fcad159","article-title":"Cerebrospinal fluid biomarkers for cerebral amyloid angiopathy","volume":"5","author":"Sembill","year":"2023","journal-title":"Brain Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/17582024.2024.2343539","article-title":"Amyloid-related imaging abnormalities (ARIA) and their radiological, biological and clinical characteristics: A plain language summary","volume":"14","author":"Hampel","year":"2024","journal-title":"Neurodegener. Dis. Manag."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology","volume":"81","author":"Ashton","year":"2024","journal-title":"JAMA Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/alz.13525","article-title":"A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer\u2019s disease","volume":"20","author":"Ferreira","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_61","unstructured":"FDA (2025, January 28). FDA Authorizes Marketing of First Blood Test to Aid in the Evaluation of Concussion in Adults, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-authorizes-marketing-first-blood-test-aid-evaluation-concussion-adults."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41582-021-00616-3","article-title":"Blood GFAP as an emerging biomarker in brain and spinal cord disorders","volume":"18","author":"Abdelhak","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/alz.12745","article-title":"Amyloid-beta misfolding and GFAP predict risk of clinical Alzheimer\u2019s disease diagnosis within 17 years","volume":"19","author":"Beyer","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1136\/jnnp-2021-328547","article-title":"Serum GFAP differentiates Alzheimer\u2019s disease from frontotemporal dementia and predicts MCI-to-dementia conversion","volume":"93","author":"Oeckl","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kim, K.Y., Shin, K.Y., and Chang, K.-A. (2023). GFAP as a Potential Biomarker for Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis. Cells, 12.","DOI":"10.3390\/cells12091309"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s13195-022-01093-6","article-title":"Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias","volume":"14","author":"Baiardi","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1001\/jamaneurol.2021.3671","article-title":"Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum","volume":"78","author":"Benedet","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13195-024-01457-0","article-title":"Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy","volume":"16","author":"Rasing","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Coppens, S., Lehmann, S., Hopley, C., and Hirtz, C. (2023). Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411624"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1212\/WNL.0000000000007767","article-title":"Plasma and CSF neurofilament light: Relation to longitudinal neuroimaging and cognitive measures","volume":"93","author":"Mielke","year":"2019","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, X., Shi, Z., Qiu, Y., Sun, D., and Zhou, H. (2024). Peripheral GFAP and NfL as early biomarkers for dementia: Longitudinal insights from the UK Biobank. BMC Med., 22.","DOI":"10.1186\/s12916-024-03418-8"},{"key":"ref_72","unstructured":"TauRx (2025, January 28). Neurofilament Light Chain (NfL). Available online: https:\/\/taurx.com\/medical-professionals\/neurofilament-light-chain-nfl."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12079-009-0068-0","article-title":"The role of osteopontin in inflammatory processes","volume":"3","author":"Lund","year":"2009","journal-title":"J. Cell Commun. Signal."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.neuroscience.2017.03.020","article-title":"Osteopontin-metallothionein I\/II interactions in experimental autoimmune encephalomyelitis","volume":"350","author":"Jakovac","year":"2017","journal-title":"Neuroscience"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1159\/000533953","article-title":"Osteopontin Is Associated with Dementia in the Presence of Cerebral Small Vessel Disease","volume":"53","author":"Ghare","year":"2024","journal-title":"Cerebrovasc. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Rosmus, D.-D., Lange, C., Ludwig, F., Ajami, B., and Wieghofer, P. (2022). The Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040840"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/alz.13474","article-title":"Associations of cortical SPP1 and ITGAX with cognition and common neuropathologies in older adults","volume":"20","author":"Lopes","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_78","first-page":"100033","article-title":"An introduction to therapeutic approaches to vascular cognitive impairment","volume":"2","author":"Hainsworth","year":"2021","journal-title":"Cereb. Circ.-Cogn. Behav."},{"key":"ref_79","first-page":"969","article-title":"Blood Biomarker Helps Distinguish Vascular Dementia","volume":"329","author":"Harris","year":"2023","journal-title":"JAMA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.blre.2016.08.004","article-title":"Placental growth factor: What hematologists need to know","volume":"31","author":"Newell","year":"2017","journal-title":"Blood Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1002\/alz.12974","article-title":"Placental growth factor as a sensitive biomarker for vascular cognitive impairment","volume":"19","author":"Hinman","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3233\/JAD-230811","article-title":"Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer\u2019s Disease","volume":"97","author":"Wu","year":"2024","journal-title":"J. Alzheimers Dis."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mammana, S., Fagone, P., Cavalli, E., Basile, M.S., Petralia, M.C., Nicoletti, F., Bramanti, P., and Mazzon, E. (2018). The Role of Macrophages in Neuroinflammatory and Neurodegenerative Pathways of Alzheimer\u2019s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis: Pathogenetic Cellular Effectors and Potential Therapeutic Targets. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030831"},{"key":"ref_84","first-page":"307","article-title":"Microglial response to amyloid plaques in APPsw transgenic mice","volume":"152","author":"Frautschy","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-immunol-093019-110159","article-title":"Microglia and Central Nervous System-Associated Macrophages-From Origin to Disease Modulation","volume":"39","author":"Prinz","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13195-020-00688-1","article-title":"Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer\u2019s disease mouse model with suppression of glymphatic clearance","volume":"12","author":"Feng","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Nabizadeh, F., Seyedmirzaei, H., and Karami, S. (2024). Neuroimaging biomarkers and CSF sTREM2 levels in Alzheimer\u2019s disease: A longitudinal study. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-66211-w"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"E19","DOI":"10.3174\/ajnr.A7586","article-title":"Amyloid-Related Imaging Abnormalities with Emerging Alzheimer Disease Therapeutics: Detection and Reporting Recommendations for Clinical Practice","volume":"43","author":"Cogswell","year":"2022","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1093\/brain\/awad188","article-title":"Amyloid-related imaging abnormalities (ARIA): Radiological, biological and clinical characteristics","volume":"146","author":"Hampel","year":"2023","journal-title":"Brain J. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.tips.2021.11.006","article-title":"Present and future of microglial pharmacology","volume":"43","author":"Vecchiarelli","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41593-021-00951-0","article-title":"Microglia contribute to the propagation of A\u03b2 Into unaffected brain tissue","volume":"25","author":"Aires","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"103917","DOI":"10.1016\/j.mcn.2024.103917","article-title":"TREM2 in Alzheimer\u2019s disease: Structure, function, therapeutic prospects, and activation challenges","volume":"128","author":"Zgorzynska","year":"2024","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3233\/JAD-221010","article-title":"Cerebrospinal Fluid sTREM-2, GFAP, and \u03b2-S100 in Symptomatic Sporadic Alzheimer\u2019s Disease: Microglial, Astrocytic, and APOE Contributions Along the Alzheimer\u2019s Disease Continuum","volume":"92","author":"Bonomi","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Park, S.-H., Lee, E.-H., Kim, H.-J., Jo, S., Lee, S., Seo, S.W., Park, H.-H., Koh, S.-H., and Lee, J.-H. (2021). The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer\u2019s disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-92101-6"},{"key":"ref_96","first-page":"160","article-title":"The Role of TREM2 in Alzheimer\u2019s Disease and Other Neurological Disorders","volume":"4","author":"Yaghmoor","year":"2014","journal-title":"J. Alzheimers Dis. Park."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7595","DOI":"10.1002\/alz.14222","article-title":"Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice","volume":"20","author":"Zhong","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_98","unstructured":"ALZFORUM (2025, January 28). Is ARIA an Inflammatory Reaction to Vascular Amyloid?. Available online: https:\/\/www.alzforum.org\/news\/conference-coverage\/aria-inflammatory-reaction-vascular-amyloid."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Chen, Y., Lu, P., Wu, S., Yang, J., Liu, W., Alzheimer\u2019s Disease Neuroimaging Initiative, Zhang, Z., and Xu, Q. (2024). CD163-Mediated Small-Vessel Injury in Alzheimer\u2019s Disease: An Exploration from Neuroimaging to Transcriptomics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042293"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1073\/pnas.0805453106","article-title":"Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy","volume":"106","author":"Hawkes","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s12974-020-01900-7","article-title":"A1 reactive astrocytes and a loss of TREM2 are associated with an early stage of pathology in a mouse model of cerebral amyloid angiopathy","volume":"17","author":"Taylor","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/bpa.12721","article-title":"Osteopontin and phospho-SMAD2\/3 are associated with calcification of vessels in D-CAA, an hereditary cerebral amyloid angiopathy","volume":"29","author":"Bulk","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12987-022-00351-x","article-title":"Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method","volume":"19","author":"Handa","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s40478-018-0540-2","article-title":"Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer\u2019s disease","volume":"6","author":"Hondius","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40478-023-01698-4","article-title":"Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients","volume":"12","author":"Vervuurt","year":"2024","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3233\/JAD-190434","article-title":"Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer\u2019s Disease Multimodal Biomarker Discovery Cohort","volume":"74","author":"Westwood","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41398-024-03075-8","article-title":"MicroRNAs: Pioneering regulators in Alzheimer\u2019s disease pathogenesis, diagnosis, and therapy","volume":"14","author":"Li","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12017-019-08568-0","article-title":"Cerebral Amyloid Angiopathy, Alzheimer\u2019s Disease and MicroRNA: MiRNA as Diagnostic Biomarkers and Potential Therapeutic Targets","volume":"21","author":"Manwani","year":"2019","journal-title":"NeuroMol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Hernandez-Rapp, J., Rainone, S., Goupil, C., Dorval, V., Smith, P.Y., Saint-Pierre, M., Vall\u00e9e, M., Planel, E., Droit, A., and Calon, F. (2016). microRNA-132\/212 deficiency enhances A\u03b2 production and senile plaque deposition in Alzheimer\u2019s disease triple transgenic mice. Sci. Rep., 6.","DOI":"10.1038\/srep30953"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.3233\/JAD-170156","article-title":"Identification of Circulating miR-125b as a Potential Biomarker of Alzheimer\u2019s Disease in APP\/PS1 Transgenic Mouse","volume":"59","author":"Hong","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/mp.2014.127","article-title":"Prognostic serum miRNA biomarkers associated with Alzheimer\u2019s disease shows concordance with neuropsychological and neuroimaging assessment","volume":"20","author":"Cheng","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Huang, X., Yuan, T., Tschannen, M., Sun, Z., Jacob, H., Du, M., Liang, M., Dittmar, R.L., Liu, Y., and Liang, M. (2013). Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-319"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.molmed.2011.06.009","article-title":"NeurimmiRs: microRNAs in the neuroimmune interface","volume":"17","author":"Soreq","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13024-021-00496-7","article-title":"The promise of microRNA-based therapies in Alzheimer\u2019s disease: Challenges and perspectives","volume":"16","author":"Walgrave","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Abidin, S.Z., Mat Pauzi, N.A., Mansor, N.I., Mohd Isa, N.I., and Hamid, A.A. (2023). A new perspective on Alzheimer\u2019s disease: microRNAs and circular RNAs. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1231486"},{"key":"ref_117","unstructured":"(2025, January 28). Hospitalization\u2013Health, United States, Available online: https:\/\/www.cdc.gov\/nchs\/hus\/topics\/hospitalization.htm."},{"key":"ref_118","unstructured":"(2025, January 28). 2023 National Population Projections Tables: Main Series, Available online: https:\/\/www.census.gov\/data\/tables\/2023\/demo\/popproj\/2023-summary-tables.html."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/4\/1070\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:06Z","timestamp":1760027346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/4\/1070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":118,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["jcm14041070"],"URL":"https:\/\/doi.org\/10.3390\/jcm14041070","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]}}}