Androgens modulate β-amyloid levels in male rat brain

Abstract

As a normal consequence of aging, men experience a significant decline in androgen levels, Although the neural consequences of age-related androgen depletion remain unclear, recent evidence suggests a link between low androgen levels and the development of Alzheimer's disease (AD), Here, we test the hypothesis that androgens act as endogenous modulators of β-amyloid protein (Aβ) levels, To investigate this possibility, brain and plasma levels of Aβ were measured in male rats with varying hormonal conditions. Depletion of endogenous sex steroid hormones via gonadectomy (GDX) resulted in increased brain levels of Aβ in comparison to gonadally intact male rats. This GDX-induced increase in Aβ levels was reversed by DHT supplementation, demonstrating a functional role for androgens in modulating brain levels of Aβ. These findings suggest that age-related androgen depletion may result in accumulation of Aβ in the male brain and thereby act as a risk factor for the development of AD.