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Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
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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“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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Metadata
- 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
- Published
- 1982-03-05
- Volume
- 215
- Issue
- 4537
- Pages
- 1237-1239
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
- 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
- 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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