A sex difference in neurodegeneration of the human hypothalamus

The mediobasal hypothalamus (MBH) of 33 males (mean age, 77 +/- 10 years) and 31 females (mean age, 78 +/- 10.3 years) was investigated for neurofibrillary pathology associated with abnormally phosphorylated tau protein. A conspicuous pathology was identified, characterized by terminal-like processes contacting the neurohemal vasculature of the posterior median eminence and the adjacent infundibular nucleus. This pathology revealed a striking sex difference: it was identified in 79% of the males, but observed in only 6% of the females. The vessel-associated neurofibrillary lesions of the mediobasal hypothalamus develop independently of Alzheimer's disease (AD)-related neocortical pathology. The sex-dependent neurofibrillary degeneration is suggested as an explanation for an impairment in neuroendocrine function previously reported in elderly men.