Cited by 961Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchExtracellular vesicles in disease

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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

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Fiandaca, Massimo S., Kapogiannis, Dimitrios, Mapstone, Mark, Boxer, Adam, Eitan, Erez, Schwartz, Janice B., Abner, Erin L., Petersen, Ronald C., Federoff, Howard J., Miller, Bruce L., Goetzl, Edward J.·2015·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2014.06.008PMC PMC4329112

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Abstract

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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Additional file 2 of Immuno-digital invasive cleavage assay for analyzing Alzheimer’s amyloid ß-bound extracellular vesicles
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Additional file 4 of Immuno-digital invasive cleavage assay for analyzing Alzheimer’s amyloid ß-bound extracellular vesicles
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Additional file 1 of Increased prediction value of biomarker combinations for the conversion of mild cognitive impairment to Alzheimer’s dementia
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Additional file 1 of Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis
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Additional file 5 of Immuno-digital invasive cleavage assay for analyzing Alzheimer’s amyloid ß-bound extracellular vesicles
Yuyama, K., Sun, H., Igarashi, Y., Monde, K., Hirase, T., Nakayama, M., & Makino, Y. (2022) · Figshare · doi:10.6084/m9.figshare.21261536
Additional file 1 of Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment
Cano, A., Antonio, E. E., Bernuz, M., Puerta, R., García‐González, P., de Rojas, I., Olivé, C., Pérez‐Cordón, A., Montrreal, L., Núñez‐Llaves, R., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22607779

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: Fiandaca, Massimo S.
Kapogiannis, Dimitrios
Mapstone, Mark
Boxer, Adam
Eitan, Erez
Schwartz, Janice B.
Abner, Erin L.
Petersen, Ronald C.
Federoff, Howard J.
Miller, Bruce L.
Goetzl, Edward J.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2014-08-14
Volume: 11
Issue: 6
Pages: 600
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2014.06.008
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case‐control study

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