Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease

Fanny M. Elahi; Kaitlin B. Casaletto; Renaud La Joie; Samantha M. Walters; Danielle Harvey; Amy Wolf; Lauren Edwards; Wilfredo Rivera-Contreras; Anna Karydas; Yann Cobigo; Howard J. Rosen; Charles DeCarli; Bruce L. Miller; Gil D. Rabinovici; Joel H. Kramer

doi:10.1016/j.jalz.2019.09.004

Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease

Fanny M. Elahi, Kaitlin B. Casaletto, Renaud La Joie, Samantha M. Walters, Danielle Harvey, Amy Wolf, Lauren Edwards, Wilfredo Rivera-Contreras, Anna Karydas, Yann Cobigo, Howard J. Rosen, Charles DeCarli, Bruce L. Miller, Gil D. Rabinovici, Joel H. Kramer

Research output: Contribution to journal › Article

4 Scopus citations

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	https://doi.org/10.1016/j.jalz.2019.09.004
State	Accepted/In press - Jan 1 2019

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

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Elahi, F. M., Casaletto, K. B., La Joie, R., Walters, S. M., Harvey, D., Wolf, A., Edwards, L., Rivera-Contreras, W., Karydas, A., Cobigo, Y., Rosen, H. J., DeCarli, C., Miller, B. L., Rabinovici, G. D., & Kramer, J. H. (Accepted/In press). Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2019.09.004

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

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. / Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease. In: Alzheimer's and Dementia. 2019.

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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.",

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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.

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KW - Late-onset Alzheimer's disease

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