Pathologic Evaluation of the Human Suprachiasmatic Nucleus in Severe Dementia

• Published in: Journal of neuropathology and experimental neurology 1999-01, Vol.58 (1), p.29-39
• Main Authors: Stopa, Edward G, Volicer, Ladislav, Kuo-Leblanc, Victoria, Harper, David, Lathi, Devayani, Tate, Barbara, Satlin, Andrew
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Analysis; Biological and medical sciences; Case-Control Studies; Circadian Rhythm - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia - pathology; Evaluation Studies as Topic; Humans; Immunohistochemistry; Male; Medical research; Medical sciences; Middle Aged; Neuroglia - pathology; Neurology; Neurons - pathology; Neuropeptide Y; Neurotensin; Parkinson disease; Suprachiasmatic Nucleus - pathology; Vasoactive intestinal peptides
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199901000-00004

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained withNissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p