# Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals

Article · Zhang S, Roemer-Cassiano SN, Chong JR, Fang T, Li Y, Wang Z, Zeng T, Li X, Deco G, Venketasubramanian N, Zhou JH, Chen CL, Lai MKP, Franzmeier N, Yeo BTT

- Archive id: doi:10.1002/alz.71891
- Published: 2026-10-01
- Venue: Alzheimer's & dementia : the journal of the Alzheimer's Association
- DOI: https://doi.org/10.1002/alz.71891
- PMID: 42811946
- PMCID: PMC13624711
- Citations: 0
- Source URL: https://doi.org/10.1002/alz.71891
- PDF: https://europepmc.org/articles/PMC13624711/pdf
- Provenance: europepmc

## Abstract

Introduction Excitation-inhibition (E/I) imbalance has been proposed as an early circuit-level mechanism in Alzheimer's disease (AD), but its relationship to molecular pathology and cognition in humans remains unclear. Methods We integrated biophysical modeling of resting-state functional magnetic resonance imaging with cerebrospinal fluid (CSF) and plasma biomarkers to examine whether E/I ratio links amyloid pathophysiology to memory in non-demented individuals across two cohorts from North America (N = 302; CSF amyloid beta 42 \[Aβ42\]) and Singapore (N = 240; plasma phosphorylated tau 217 \[p-tau217\]). Results Elevated E/I ratio was associated with lower CSF Aβ42 and higher plasma p-tau217, with greater sensitivity in sensory-motor regions. In contrast, elevated E/I ratio in association cortices was more strongly related to worse memory function. Mediation analyses indicated E/I ratio partially accounted for the AD biomarker-memory relationship. Discussion E/I imbalance represents an intermediate, systems-level circuit mechanism that links AD pathophysiology to cognitive impairment, offering novel insight into early neurophysiological changes along the AD continuum.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Alzheimer's, Parkinson's & Neurodegeneration](https://space-kitty.com/topics/neurodegeneration)

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