Hormonal regulation for the prevention of cognitive decline of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia, with its two pathological hallmarks being the abnormal accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau, leading to neuronal degradation. Aging is known to be the number one contributing risk factor for AD, with reproductive senescence proving a clear driver for pathological development. Luteinizing hormone (LH) has become a recent subject of research for its role in the etiology of AD, with LH levels jumping upon reproductive senescence. Recent evidence suggests that LH serves as a novel target for dementia treatment, including AD. We hypothesized that AD pathology and memory deficits will be prevented by the reduction of LH levels via a novel adeno-associated virus (AAV) vector treatment in female APP/PS1 mice. In the current study, AAV-mediated anti-LH antibody treatment was tested to investigate its ability to prevent cognitive decline and AD pathologies in the APP/PS1 mouse model of AD. We investigated changes in locomotor activity, short-term working memory, anxiety-like behaviors, and hippocampal-dependent spatial reference memory and learning. Additionally, the ability for AAV-mediated anti-LH antibody treatment to prevent the AD pathologies Aβ plaques and hyperphosphorylated tau was investigated. This work contributes to a growing body of evidence which suggests a therapeutic potential for targeting elevated LH levels in the prevention or treatment of AD.