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Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case‐control study
Open accessAbstract
Background: Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods: Blood exosomes obtained at one time‐point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time‐points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD‐pathogenic exosomal proteins were extracted and quantified by enzyme‐linked immunosorbent assays. Results: Mean exosomal levels of total tau, P‐T181‐tau, P‐S396‐tau, and amyloid β 1–42 (Aβ1–42) for AD and levels of P‐T181‐tau and Aβ1–42 for FTD were significantly higher than for case‐controls. Step‐wise discriminant modeling incorporated P‐T181‐tau, P‐S396‐tau, and Aβ1–42 in AD, but only P‐T181‐tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P‐S396‐tau, P‐T181‐tau, and Aβ1–42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD. Conclusions: Levels of P‐S396‐tau, P‐T181‐tau, and Aβ1–42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.
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“Altered EV profiles are detectable at prodromal stages such as MCI, supporting their value as early biomarkers. 26 , 27”
From Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [26]
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“Exosomes isolated from the brain, cerebrospinal fluid (CSF), and plasma of AD patients and/or AD animal models contain pathologic Aβ and tau [73, 75–77].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [77]
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“Interestingly, increased levels of exosome-associated tau have been found by some groups in the CSF and blood of individuals with AD and FTDs [55, 117].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [117]
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Metadata
- Authors
- Fiandaca, M. S., Kapogiannis, D., Mapstone, M., Boxer, A., Eitan, E., Schwartz, J. B., Abner, E. L., Petersen, R. C., Federoff, H. J., Miller, B. L., & Goetzl, E. J.
- Affiliations
- Georgetown University Medical Center (US)
- National Institute on Aging (US)
- University of Rochester Medicine (US)
- University of California San Francisco Medical Center (US)
- University of Kentucky (US)
- Mayo Clinic (US)
- Corresponding author
- Goetzl, Edward J.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-08-14
- Volume
- 11
- Issue
- 6
- Pages
- 600
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4329112
- OpenAlex
- W1995903088
- Cited by
- 959
- References
- 31
- Citations by year
- 2026: 77 · 2025: 91 · 2024: 109 · 2023: 86 · 2022: 115 · 2021: 106 · 2020: 105 · 2019: 93 · 2018: 46 · 2017: 50 · 2016: 50 · 2015: 24 · 2014: 3
- FWCI
- 28.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (NIA RO1AG030753)
- National Institutes of Health (UK ADC P30 AG028383)
- Genentech
- Alzheimer's Association
- Association for Frontotemporal Degeneration
- Alzheimer's Drug Discovery Foundation
- Pfizer
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- preclinical Alzheimer's disease, blood exosomes
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Peptide Fragments, Phosphorylation, Retrospective Studies, Severity of Illness Index, Time Factors, Biomarkers, Discriminant Analysis, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Exosomes, Frontotemporal Dementia, Prodromal Symptoms
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