AMPA-selective glutamate receptor subtype immunoreactivity in the entorhinal cortex of non-demented elderly and patients with Alzheimer's disease.
The present work employed immunocytochemical techniques and examined the distribution and cytological features of the AMPA receptor subunits, GluR2/3 and GluR1 within the entorhinal cortex of non-demented elderly (NC), patients with neuropathological and clinical verification of Alzheimer's disease (AD) and patients without a clinical history of dementia yet exhibiting sufficient quantities of senile plaques to meet neuropathological criteria of Alzheimer's disease (HPND). In NC cases, GluR2/3-immunolabeled neurons were abundantly distributed throughout layers II, III, V and VI of the entorhinal cortex. In contrast, GluR1-positive cells were comparatively sparse in number and largely restricted to layers V and VI. In AD, GluR2/3- and GluR1-labeled neurons were markedly reduced. Similarly, adjacent Nissl-stained tissue sections revealed substantial cell loss in the entorhinal cortex thus providing a reasonable explanation for the loss of these receptor subunits. Importantly, a dramatic loss of GluR2/3- and GluR1-immunolabeled neurons is also observed in the HPND cases, although examination of Nissl-stained tissue sections reveals little if any evidence of cell loss. The latter data suggest that a 'down-regulation' of these receptor subunits occurs prior to the actual loss of these cells. Furthermore, we hypothesize that the decrease of specific AMPA receptor subunits may influence neuronal vulnerability via a mechanism involving increased intracellular calcium and the destabilization of intracellular calcium homeostasis.
Armstrong
D M
DM
FIDIA-Georgetown Institute for the Neurosciences, Georgetown University, Washington, DC 20007.
Ikonomovic
M D
MD
Sheffield
R
R
Wenthold
R J
RJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D018091:Receptors, AMPA / Q000276:immunology / Q000378:metabolism*
D018091:Receptors, AMPA; D002118:Calcium