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July 1, 1998

Abnormalities of neural circuitry in Alzheimer's disease
Hippocampus and cortical cholinergic innervation

Changiz Geula, PhDAuthors Info & Affiliations
July 1998 issue
51 (1_suppl_1) S18-S29
https://doi.org/10.1212/WNL.51.1_Suppl_1.S18
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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 the 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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Information & Authors

Information

Published In

Neurology®
Volume 51 • Number 1_suppl_1 • July 1998
Pages: S18-S29
PubMed: 9674759

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© 1998.

Publication History

Published online: July 1, 1998
Published in print: July 1998

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Affiliations & Disclosures

Changiz Geula, PhD
From the Laboratory for Neurodegenerative and Aging Research, Section of Gerontology, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA.
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Notes

Address correspondence and reprint requests to Dr. Changiz Geula, Laboratory for Neurodegenerative and Aging Research, Beth Israel Deaconess Medical Center, 21-27 Burlington Avenue, PO Box 15709, Boston, MA 02215.

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