Journal
ALZHEIMERS & DEMENTIA
Volume 16, Issue 4, Pages 681-695Publisher
WILEY
DOI: 10.1016/j.jalz.2019.09.004
Keywords
Early-onset Alzheimer's disease; Late-onset Alzheimer's disease; Cerebral small vessel disease; Astrocytopathy; Immune activation; Inflammation; Brain homeostasis; Growth hormones; Exosomes; White matter disease; Neurodegeneration
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Funding
- National Institute on Aging (NIA) [U24 AG21886]
- NIH-NIA ADRC [P50 AG023501]
- NIH-NIA PPG [P01AG019724]
- Larry L. Hillblom Network Grant [2014-A-004-NET]
- American Academy of Neurology grant
- Alzheimer's Association
- [AG058752]
- [AG045611]
- [AG032289]
- [AG048234]
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Introduction: We investigated plasma proteomic markers of astrocytopathy, brain degeneration, plasticity, and inflammation in sporadic early-onset versus late-onset Alzheimer's disease (EOAD and LOAD). Methods: Plasma was analyzed using ultra-sensitive immuno-based assays from 33 EOAD, 30 LOAD, and 36 functionally normal older adults. Results: Principle component analyses identified 3 factors: trophic (BDNF, VEGF, TGF beta), degenerative (GFAP, NfL), and inflammatory (TNF alpha, IL-6, IP-10, IL-10). Trophic factor was elevated in both AD groups and associated with cognition and gray matter volumes. Degenerative factor was elevated in EOAD, with higher levels associated with worse functioning in this group. Biomarkers of inflammation were not significantly different between groups and were only associated with age. Disucssion: Plasma proteomic biomarkers provide novel means of investigating molecular processes in vivo and their contributions to clinical outcomes. We present initial investigations of several of these fluid biomarkers, capturing aspects of astrocytopathy, neuronal injury, cellular plasticity, and inflammation in EOAD versus LOAD.
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