Hyperactivity of subicular parvalbumin interneurons drives early amyloid pathology and cognitive deficits in Alzheimer's disease.

ABSTRACT: Atrophy of the subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (AD) and is closely associated with early cognitive decline. However, the underlying mechanisms driving this vulnerability remain unclear. In this study, using the 5×FAD mouse model, we identified significant amyloid-beta (Aβ) accumulation in the subiculum during the early stages of AD. Through a combination of laser microdissection and proteomic analysis, we uncovered early dysregulation of GABAergic neurons in the subiculum. Further investigation revealed that parvalbumin (PV) interneurons (PV-INs) were key drivers of Aβ pathology, exhibiting pronounced hyperactivity during the initial stages of AD. Targeted inhibition of this PV interneuron hyperactivity at the onset of AD, using chemogenetic a

SUBMITTER: Chen YB 

PROVIDER: S-EPMC12602357 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature