ALZHEIMER’S AND DEMENTIA

Elahi FM, Casaletto KB, La Joie R, Walters SM, Harvey D, Wolf A, Edwards L, Rivera-Contreras W, Karydas A, Cobigo Y, Rosen HJ, DeCarli C, Miller BL, Rabinovici GD and Kramer JH.

Alzheimers Dement. 2019 Dec 23. pii: S1552-5260(19)35373-7

doi: 10.1016/j.jalz.2019.09.004

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.

Discussion

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.