Abnormalities of neural circuitry in Alzheimer's disease: Hippocampus and cortical cholinergic innervation
Abstract
Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.
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Cholinergic degeneration is a major clinical feature of both age-related cognitive decline and Alzheimer's dementia.
“with cholinergic degeneration a major clinical feature of both age-related cognitive decline and Alzheimer’s dementia [16,17].”
From Systematic Overview of Bacopa monnieri (L.) Wettst. Dominant Poly-Herbal Formulas in Children and Adolescents (2017) · cites this paper as [16]
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“These findings show promise for ageing research, with cholinergic degeneration a major clinical feature of both age-related cognitive decline and Alzheimer’s dementia [16,17].”
BackgroundPropagation of TDP-43 proteinopathy in neurodegenerative disorders
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Self-citation
- Authors
- Geula, C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Geula, Changiz
- ORCID
- Geula, Changiz
- Venue
- Neurology
- Published
- 1998-07
- Volume
- 51
- Issue
- 1_suppl_1
- Pages
- S18-29; discussion S65
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2146593685
- Cited by
- 184
- References
- 76
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 10 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 3
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bayer Corporation
- National Institute on Aging (AG 10282, R29AG010282)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, cortical circuits, cholinergic system, memory loss, neurofibrillary tangles, neuronal loss, selective vulnerability, early diagnosis, preclinical Alzheimer's disease, cognitive impairment, therapeutic implications
- MeSH terms
- Alzheimer Disease, Cerebral Cortex, Cholinergic Fibers, Hippocampus, Humans, Neural Pathways
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