Sex-dependent cytoskeletal changes of the human hypothalamus develop independently of Alzheimer's disease

This study examines a sex-dependent variant; of neurofibrillary pathology r ecently identified in the hypothalamus of elderly human males. Here we focu s upon the relationship between the sex-dependent hypothalamic changes and Alzheimer's disease (AD)-related neurofibrillary pathology. To this end, au topsy brains of 31 males (mean age 84.1 years) and 26 age-matched females ( mean age 86.7 years) were examined. Both the male and the female subjects e xhibited either particularly mild (stage I) or fully developed (stage V) AD -related neurofibrillary brain pathology Serial 100-mu m hypothalamic secti ons were cut in the frontal plane and stained for hyperphosphorylated tau p rotein using the monoclonal antibody AT8. Argyrophilic neurofibrillary path ology was demonstrated using a modified Gallyas silver-iodide technique. A conspicuous pathology, characterized by neurofibrillary tangles, a network of dystrophic neurites, and terminal-like vessel-associated processes, was identified in the infundibular nucleus which is located in the mediobasal t uber cinereum. This pathology was noted in 20 males (64.5%), but did not oc cur in. the female group. No statistically significant correlation was note d between the degree of sex-dependent pathology and the presence of AD-rela ted cortical pathology. In particular, the expression of the sex-dependent changes did not differ between males with AD stage I and males with AD stag e V In summary, the existence of a sex-dependent variant of neurofibrillary pathology was confirmed. In addition, our findings strongly suggest that t he sex-dependent changes develop independently of the neurofibrillary chang es associated with senile dementia of the Alzheimer type. Instead, the sex- dependent hypothalamic pathology probably corresponds to a distinct neurode generative entity preferentially affecting elderly males. (C) 1999 Academic Press.