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Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome
Open accessAbstract
Introduction: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non‐AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated‐tau in neuronal exosomes may document preclinical AD. Methods: AD neuropathogenic proteins Aβ 1–42, P‐T181‐tau, and P‐S396‐tau were quantified by enzyme‐linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age‐matched controls. Results: Neuronal exosome levels of Aβ 1–42, P‐T181‐tau, and P‐S396‐tau were significantly elevated in individuals with DS compared with age‐matched controls at all ages beginning in childhood. No significant gender differences were observed. Discussion: These early increases in Aβ 1–42, P‐T181‐tau, and P‐S396‐tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.
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“The rationale for using plasma biomarkers as proxies for brain processes [173] has been demonstrated for multiple neurodegenerative diseases [174, 175].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [174]
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Self-citation
Metadata
- Authors
- Hamlett, E. D., Goetzl, E. J., Ledreux, A., Vasilevko, V., Boger, H. A., LaRosa, A., Clark, D., Carroll, S. L., Carmona‐Iragui, M., Fortea, J., Mufson, E. J., Sabbagh, M., Mohammed, A. H., Hartley, D., Doran, E., Lott, I. T., & Granholm, A.
- Affiliations
- University of Denver (US)
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Medical University of South Carolina (US)
- Hospital de Sant Pau (ES)
- Barrow Neurological Institute (US)
- Linnaeus University (SE)
- Alzheimer's Association (US)
- Corresponding author
- Granholm, Ann‐Charlotte
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-10-15
- Volume
- 13
- Issue
- 5
- Pages
- 541-549
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5812672
- OpenAlex
- W2537024319
- Cited by
- 129
- References
- 47
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 19 · 2020: 17 · 2019: 25 · 2018: 15 · 2017: 9
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - DU (University of Denver) (submittedVersion)
- Funders
- National Institutes of Health (R01AG 21912, R01HD065160, RO1AG04375, PO1AG14449)
- National Center for Research Resources
- National Center for Advancing Translational Sciences (UL1 TR000153)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- Down syndrome, Alzheimer's disease
- MeSH terms
- Adolescent, Alzheimer Disease, Down Syndrome, Female, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Exosomes, Young Adult
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