Parvalbumin as a sex-specific target in Alzheimer’s disease research – A mini-review

Abstract

Alzheimer’s disease (AD) is the most common form of dementia, and both the incidence of this disease and its associated cognitive decline disproportionally effect women. While the etiology of AD is unknown, recent work has demonstrated that the balance of excitatory and inhibitory activity across the brain may serve as a strong predictor of cognitive impairments in AD. Across the cortex, the most prominent source of inhibitory signalling is from a class of parvalbumin-expressing interneurons (PV+). In this mini-review, the impacts of sex- and age-related factors on the function of PV+ neurons are examined within the context of vulnerability to AD pathology. These primary factors of influence include changes in brain metabolism, circulating sex hormone levels, and inflammatory response. In addition to positing the increased vulnerability of PV+ neurons to dysfunction in AD, this mini-review highlights the critical importance of presenting sex stratified data in the study of AD.