Abstract
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, TGFβ), degenerative (GFAP, NfL), and inflammatory (TNFα, 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.
| Original language | English (US) |
|---|---|
| Journal | Alzheimer's and Dementia |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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Keywords
- Astrocytopathy
- Brain homeostasis
- Cerebral small vessel disease
- Early-onset Alzheimer's disease
- Exosomes
- Growth hormones
- Immune activation
- Inflammation
- Late-onset Alzheimer's disease
- Neurodegeneration
- White matter disease
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
Cite this
Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease. / Elahi, Fanny M.; Casaletto, Kaitlin B.; La Joie, Renaud; Walters, Samantha M.; Harvey, Danielle; Wolf, Amy; Edwards, Lauren; Rivera-Contreras, Wilfredo; Karydas, Anna; Cobigo, Yann; Rosen, Howard J.; DeCarli, Charles; Miller, Bruce L.; Rabinovici, Gil D.; Kramer, Joel H.
In: Alzheimer's and Dementia, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease
AU - Elahi, Fanny M.
AU - Casaletto, Kaitlin B.
AU - La Joie, Renaud
AU - Walters, Samantha M.
AU - Harvey, Danielle
AU - Wolf, Amy
AU - Edwards, Lauren
AU - Rivera-Contreras, Wilfredo
AU - Karydas, Anna
AU - Cobigo, Yann
AU - Rosen, Howard J.
AU - DeCarli, Charles
AU - Miller, Bruce L.
AU - Rabinovici, Gil D.
AU - Kramer, Joel H.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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, TGFβ), degenerative (GFAP, NfL), and inflammatory (TNFα, 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.
AB - 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, TGFβ), degenerative (GFAP, NfL), and inflammatory (TNFα, 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.
KW - Astrocytopathy
KW - Brain homeostasis
KW - Cerebral small vessel disease
KW - Early-onset Alzheimer's disease
KW - Exosomes
KW - Growth hormones
KW - Immune activation
KW - Inflammation
KW - Late-onset Alzheimer's disease
KW - Neurodegeneration
KW - White matter disease
UR - http://www.scopus.com/inward/record.url?scp=85076981263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076981263&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2019.09.004
DO - 10.1016/j.jalz.2019.09.004
M3 - Article
AN - SCOPUS:85076981263
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
ER -