Molecular and neuropathological determinants of neuronal dysfunction in Alzheimer's disease.

ABSTRACT: The biological basis of neuronal excitatory/inhibitory (E/I) imbalance in Alzheimer's disease (AD) remains unclear. Using a comprehensive cohort with ante-mortem functional neuroimaging and post-mortem molecular data from the same participants, we mapped individual, whole-brain E/I imbalances through biophysical modeling. E/I ratios in regions supporting higher-order cognitive functions were significantly associated with cognitive performance and decline, with mediation by global neuropathological burden. We also observed a significant inverted U-shaped relationship between E/I ratios and neurofibrillary tangle severity, peaking at the limbic stage (Braak III-IV) in 14 brain areas, including the bilateral hippocampus and superior frontal gyrus. In addition, we identified 89 genes and 101 p

SUBMITTER: Sanchez-Rodriguez LM 

PROVIDER: S-EPMC12632611 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature