Single-cell peripheral immunoprofiling of Alzheimer's and Parkinson's diseases.

Abstract:

:Peripheral blood mononuclear cells (PBMCs) may provide insight into the pathogenesis of Alzheimer's disease (AD) or Parkinson's disease (PD). We investigated PBMC samples from 132 well-characterized research participants using seven canonical immune stimulants, mass cytometric identification of 35 PBMC subsets, and single-cell quantification of 15 intracellular signaling markers, followed by machine learning model development to increase predictive power. From these, three main intracellular signaling pathways were identified specifically in PBMC subsets from people with AD versus controls: reduced activation of PLCγ2 across many cell types and stimulations and selectively variable activation of STAT1 and STAT5, depending on stimulant and cell type. Our findings functionally buttress the now multiply-validated observation that a rare coding variant in PLCG2 is associated with a decreased risk of AD. Together, these data suggest enhanced PLCγ2 activity as a potential new therapeutic target for AD with a readily accessible pharmacodynamic biomarker.

journal_name

Sci Adv

journal_title

Science advances

authors

Phongpreecha T,Fernandez R,Mrdjen D,Culos A,Gajera CR,Wawro AM,Stanley N,Gaudilliere B,Poston KL,Aghaeepour N,Montine TJ

doi

10.1126/sciadv.abd5575

subject

Has Abstract

pub_date

2020-11-25 00:00:00

issue

48

issn

2375-2548

pii

6/48/eabd5575

journal_volume

6

pub_type

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