Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain

Whitehouse, PJ; Price, DL; Struble, RG; Clark, AW; Coyle, JT; DeLong, Mahlon R.

doi:10.1126/science.7058341

Cited by 3,627Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain

Whitehouse, PJ, Price, DL, Struble, RG, Clark, AW, Coyle, JT, DeLong, Mahlon R.·1982·Science

DOI 10.1126/science.7058341

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Abstract

Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.

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Sst interneurons mediate the effects of arousal in cortical circuits under the effects of acetylcholine, which is also highly disrupted early in AD through the loss of cholinergic neurons in the basal forebrain.
“Furthermore, they mediate the effects of arousal in cortical circuits92 under the effects of acetylcholine, which is also highly disrupted early in AD through the loss of cholinergic neurons in the basal forebrain93.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [93]

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Authors: Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R.
Affiliations: Johns Hopkins University (US)
Neuropathology Laboratory, Departments of Pathology and Neurology, Baltimore, Maryland 21205
Departments of Pharmacology and Experimental Therapy, Psychiatry, and Neuroscience, Baltimore, Maryland 21205
ORCID: DeLong, Mahlon R.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1982-03-05
Volume: 215
Issue: 4537
Pages: 1237-1239
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7058341
OpenAlex: W2093374391
Semantic Scholar: e0380e88fdffd5a546eb76a1d2eb7d05db143f94
Cited by: 3,627
References: 44
Citations by year: 2026: 52 · 2025: 42 · 2024: 53 · 2023: 67 · 2022: 62 · 2021: 91 · 2020: 95 · 2019: 66 · 2018: 63 · 2017: 66 · 2016: 82 · 2015: 65 · 2014: 73 · 2013: 63 · 2012: 56
FWCI: 110.00
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Alzheimer's disease, senile dementia, nucleus basalis of Meynert, basal forebrain, cholinergic neurons, neuronal loss, cholinergic deficit, cerebral cortex, presynaptic markers, subcortical lesions
MeSH terms: Acetylcholine, Alzheimer Disease, Basal Ganglia, Dementia, Humans, Neural Pathways

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Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain

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