Cited by 265Circadian rhythm and melatoninAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Pathologic Evaluation of the Human Suprachiasmatic Nucleus in Severe Dementia

Stopa, Edward G., Volicer, Ladislav, Kuo-Leblanc, Victoria, Harper, David, Lathi, Devayani, Tate, Barbara, Satlin, Andrew·1999·Journal of Neuropathology and Experimental Neurology

DOI 10.1097/00005072-199901000-00004

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Abstract

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 with: Nissl, 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 < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.

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Authors: Stopa, E. G., Volicer, L., Kuo-Leblanc, V., Harper, D., Lathi, D., Tate, B., & Satlin, A.
Affiliations: Harvard University (US)
Brown University (US)
Edith Nourse Rogers Memorial Veterans Hospital (US)
Corresponding author: Stopa, Edward G.
ORCID: Volicer, Ladislav
Harper, David
Tate, Barbara
Satlin, Andrew
Venue: Journal of Neuropathology and Experimental Neurology
Publisher: Oxford University Press (OUP)
Published: 1999-01
Volume: 58
Issue: 1
Pages: 29-39
ISSN: 0022-3069 (ISSN-L)
DOI: 10.1097/00005072-199901000-00004
OpenAlex: W1965668843
Cited by: 265
References: 0
Citations by year: 2026: 8 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 7 · 2021: 19 · 2020: 20 · 2019: 10 · 2018: 13 · 2017: 11 · 2016: 16 · 2015: 9 · 2014: 11 · 2013: 10 · 2012: 14
FWCI: 1.77
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neuropathology & Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag009301-08, 5r01ag010682-06)
National Institute on Aging (AG10682, AG-09301)
National Institute of Mental Health (MH.NS 31862)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: suprachiasmatic nucleus, advanced dementia, Alzheimer's disease, circadian rhythm disruption, sleep disruption, vasopressin neurons, neurofibrillary tangles, neurodegeneration, hypothalamus, Pick's disease, hippocampal sclerosis, Parkinson's disease
MeSH terms: Circadian Rhythm, Dementia, Evaluation Studies as Topic, Humans, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neurons, Suprachiasmatic Nucleus, Case-Control Studies

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Pathologic Evaluation of the Human Suprachiasmatic Nucleus in Severe Dementia

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