The cholinergic system exerts opposing effects on memory at different stages of disease progression in Alzheimer's and Down syndrome model systems.

ABSTRACT:

Introduction

The long-standing cholinergic hypothesis posits that cholinergic signaling is uniformly deficient in Alzheimer's disease (AD) and Down syndrome (DS). We tested the hypothesis that this deficiency occurs primarily late in disease, while early stages involve excessive cholinergic signaling, with distinct implications for memory.

Methods

Tg2576 (AD model; n = 38), Ts65Dn (DS model; n = 14), and wild-type (WT; n = 17) mice at young (3 to 4 months) and old (>14 months) ages received treatments to reduce cholinergic signaling (medial septum chemogenetic inhibition, muscarinic antagonist scopolamine) or enhance it (acetylcholinesterase inhibitor donepezil). Memory assessments used novel object recognition.

Results

Anticholinergic manipulations restored memory in

SUBMITTER: Lisgaras CP 

PROVIDER: S-EPMC12921640 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature