Increased excitatory to inhibitory synaptic ratio in parietal cortex samples from individuals with Alzheimer's disease.

ABSTRACT: Synaptic disturbances in excitatory to inhibitory (E/I) balance in forebrain circuits are thought to contribute to the progression of Alzheimer's disease (AD) and dementia, although direct evidence for such imbalance in humans is lacking. We assessed anatomical and electrophysiological synaptic E/I ratios in post-mortem parietal cortex samples from middle-aged individuals with AD (early-onset) or Down syndrome (DS) by fluorescence deconvolution tomography and microtransplantation of synaptic membranes. Both approaches revealed significantly elevated E/I ratios for AD, but not DS, versus controls. Gene expression studies in an independent AD cohort also demonstrated elevated E/I ratios in individuals with AD as compared to controls. These findings provide evidence of a marked pro-excitatory

SUBMITTER: Lauterborn JC 

PROVIDER: S-EPMC8110554 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature