Somatostatin 1-12 immunoreactivity is decreased in the hypothalamic lateral tuberal nucleus of Huntington's disease patients.

The hypothalamic lateral tuberal nucleus (NTL) can be recognized in man and higher primates, only. The function of this nucleus is unknown, but the NTL is affected in a variety of human neurodegenerative diseases, including Huntington's disease (HD) and Alzheimer's disease. In the present study we demonstrate an abundant presence of somatostatin 1-12 (SST1-12) immunoreactivity in both neurites and perikarya of the NTL. This immunoreactivity could be visualized best after microwave pretreatment. In HD brains, NTL SST1-12 immunoreactivity was greatly reduced, providing further evidence of the presence of SST1-12 as an intrinsic neuropeptide in the NTL. Although striatal SST neurons escape destruction in HD, our study demonstrates that not all SST neurons are resistant to the degenerative process in this disease.

Lewy bodies in the lateral hypothalamus: do they imply neuronal loss?

Lewy bodies have been found in the hypothalamic lateral tuberal nucleus (NTL) and the adjoining tuberomammillary nucleus (TM) in Parkinson's disease (PD). The NTL is severely atrophic in Huntington's disease; the TM seems unaffected. In this study, we examined the NTL and the TM of seven PD patients and one patient with presumed PD to assess whether the presence of Lewy bodies indicated neuronal loss. Most Lewy bodies were found in the TM, but they were also present in the NTL of seven of the eight patients. The number of NTL neurons in the PD patients was similar to a group of 14 nonneurological controls, seven Alzheimer's disease (AD) patients, and two AIDS patients with dementia. This challenges the hypothesis that Lewy bodies are a sign of significant cell death. The TM, whose cells could not be counted, did not seem depleted in neuronal numbers, although occasional neuronophagia was observed.

Tau and ubiquitin in the human hypothalamus in aging and Alzheimer's disease.

Immunocytochemical staining of hypothalamic cell groups with four antibodies to Alzheimer paired helical filaments (PHF) (i.e., anti-PHF serum 60e and monoclonal antibody (mAb) Alz-50, both directed against normal and abnormally phosphorylated tau; mAb tau-1, which recognizes tau; and mAb 3-39 to PHF, which recognizes the carboxy terminal domain of ubiquitin) revealed a clear distinction between 12 Alzheimer's disease (AD) patients and seven controls in the hypothalamus. Dystrophic neurites, which appeared to be the most specific components in AD, were most conspicuous after Alz-50 staining. However, Alz-50 also stained neuronal cytoplasm and normal, thin, beaded neurites in the paraventricular nucleus (PVN) of controls, even of young cases. This staining was clearly distinct from the staining of cytoplasm and dystrophic neurites in the PVN of Alzheimer patients. The abundant staining of dystrophic neurites and cell bodies in the nucleus tuberalis lateralis (NTL) in AD, in which no neuronal loss is observed, suggests that alterations in cytoskeletal markers do not necessarily indicate impending cell death. Moreover, the cytoskeletal changes in the NTL, sexually dimorphic and suprachiasmatic nuclei in AD indicate that this condition is not restricted to cortical areas or nuclei projecting to the cortex. Consequently, the pathophysiological implications of cytoskeletal staining in AD are at present far from clear. The human hypothalamus may not only provide a better insight into the pathogenesis of Alzheimer's disease, but could also be of help in the neuropathological diagnosis of this condition.