Sex differences in androgen receptor immunoreactivity in basal forebrain nuclei of elderly and Alzheimer patients

The vertical limb of the diagonal band of Broca (VDB or Ch2) and the nucleus basalis of Meynert (NBM or Ch4) are major cholinergic nuclei of the human basal forebrain, a complex that is affected in Alzheimer's disease (AD). Sex hormones influence the function of these cholinergic neurons in animals and humans and we showed earlier that estrogen and androgen receptors (AR) are present in both the VDB and the NBM of young patients of 20-39 years of age. The aim of the present study was to investigate whether AR expression changes in relation to aging and AD. In both brain areas of male and female patients over the age of 56 nuclear staining had almost disappeared and cytoplasmic AR expression was decreased. This decrease was most pronounced in the VDB of men. In addition, the proportion of neurons showing cytoplasmic AR expression was higher in control aged women than in control aged men in both the VDB and the NBM. Surprisingly, cytoplasmic ARs were significantly decreased in the VDB and the NBM only in AD women and not in AD men. These observations suggest the possible involvement of androgens in the functional changes of the basal forebrain nuclei in aging and AD.