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Deficient glutamate tranport is associated with neurodegeneration in Alzheimer's disease
Author(s) -
Masliah E.,
Hansen L.,
Alford M.,
Deteresa R.,
Mallory M.
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410400512
Subject(s) - neurodegeneration , glutamate receptor , alzheimer's disease , neuroscience , medicine , disease , psychology , receptor
The mechanisms of synapse damage in Alzheimer's disease (AD) are not fully understood. Deficient functioning of glutamate transporters might be involved in synaptic pathology and neurodegeneration by failing to clear excess glutamate at the synaptic cleft. In AD, glutamate transporter activity as assessed by D‐[ 3 H]aspartate binding is decreased; however, it is not clear to what extent it is associated with the neurodegenerative process and cognitive alterations. For this purpose, levels of D‐ and L‐[ 3 H]asparate binding in midfrontal cortex were correlated with synaptophysin levels, brain spectrin degradation product levels, and clinical and neuropathological indicators of AD. Compared to control brains AD brains displayed a 34% decrease in levels of D‐[ 3 H]aspartate binding, a 30% decrease in L‐[ 3 H]aspartate binding, and a 48% loss of synaptophysin immunoreactivity. Increased levels of brain spectrin degradation products correlated with a decrease in levels of D‐[ 3 H] and L‐[ 3 H]aspartate binding, and decreased levels of synaptophysin immuno‐reactivity. Levels of L‐[ 3 H]asparatate binding correlated with levels of synaptophysin immunoreactivity. These results suggest that decreased glutamate transporter activiyt in AD is associated with increased excitotoxicity and neurodegeneration, supporting the possibility that abnormal functioning of this system might be involved in the pathogenesis of synaptic damage in AD.