Defects of Immune Regulation in the Presenilin-1 Mutant Knockin Mouse

Overview

Journal Neuromolecular Med

Specialty Biochemistry

Date 2006 Nov 23

PMID 17114823

Citations 5

Authors

Grant A Morgan

Qing Guo

Sic L Chan

Devin S Gary

Barbara A Osborne

Mark P Mattson

Affiliations

Soon will be listed here.

Abstract

Mutations in the presenilin-1 (PS1) gene are causally linked to early-onset Alzheimer's disease (AD). Studies of neurons suggest that PS1 mutations result in a gain-of-function, which perturbs calcium regulation and increases cell vulnerability to apoptosis. Alterations in immune cell function have also been demonstrated in AD, and a role for PS1 in immune regulation has been suggested recently. We now report that splenocytes from PS1-mutant (M146V) knockin mice exhibit increased caspase activity, abnormal calcium regulation and aberrant mitochondrial function. Isolated splenic T cells from PS1-mutant mice respond poorly to proliferative signals and have downregulated cluster designation 3 and interleukin (IL)- 2-receptor expression necessary for a normal T-cell immune response. Thus, adverse effects of a mutation that causes AD on immune function that involves perturbed calcium regulation and cytokine signaling in lymphocytes, and associated sensitivity of lymphocytes to apoptosis are demonstrated. These findings suggest that abnormalities in immune function might play major roles in the pathogenesis of AD.

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