Mechanisms of synaptic dysfunction in Alzheimer's disease.
Year: 1995
Type: article
Abstract: Alzheimer's disease (AD) is characterized by a progressive cognitive decline in which memory, initiation, learning and conceptualization are severely affected. The main histopathological alterations are the presence of amyloid beta/A4-containing plaques, tangles and amyloid angiopathy. It is believed that these brain alterations are associated with abnormal expression and/or processing of amyloid precursor protein (APP) and with abnormal assembly of cytoskeletal proteins. Recent quantitative studies with the electron microscope and with immunochemical/immunocytochemical assays, using molecular markers for synaptic proteins, have shown that synaptic loss in the cortex is the major correlate of the patterns of cognitive decline in AD. The synaptic loss in AD is accompanied by neuronal loss and aberrant sprouting, and studies in incipient AD cases have shown that this alteration occurs very early in the progression of the disease preceding tangle formation and neuronal loss. These results suggest that damage to the synaptic terminal plays a central role in the pathogenesis of AD. The mechanisms of synaptic pathology in AD are not yet clear, however, studies in transgenic animal models support the possibility that APP participates in synaptic stabilization and that abnormal metabolism of this molecule could lead to synaptic dysfunction which, in turn, results in neurodegeneration and dementia.
Source: PubMed
Author: E Masliah
Institution: University of California San Diego
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: National Institute on Aging
OpenAlex ID: W2401309054