In Alzheimer’s disease (AD), synaptic alterations play a major role and are often correlated with cognitive
changes. In order to better understand synaptic modifications, we compared alterations in NMDA receptors and postsynaptic
protein PSD-95 expression in the entorhinal cortex (EC) and frontal cortex (FC; area 9) of AD and control brains.
We combined immunohistochemical and image analysis methods to quantify on consecutive sections the distribution of
PSD-95 and NMDA receptors GluN1, GluN2A and GluN2B in EC and FC from 25 AD and control cases. The density of
stained receptors was analyzed using multivariate statistical methods to assess the effect of neurodegeneration. In both regions,
the number of neuronal profiles immunostained for GluN1 receptors subunit and PSD-95 protein was significantly
increased in AD compared to controls (3-6 fold), while the number of neuronal profiles stained for GluN2A and GluN2B
receptors subunits was on the contrary decreased (3-4 fold). The increase in marked neuronal profiles was more prominent
in a cortical band corresponding to layers 3 to 5 with large pyramidal cells. Neurons positive for GluN1 or PSD-95 staining
were often found in the same localization on consecutive sections and they were also reactive for the anti-tau antibody
AD2, indicating a neurodegenerative process. Differences in the density of immunoreactive puncta representing neuropile
were not statistically significant. Altogether these data indicate that GluN1 and PSD-95 accumulate in the neuronal perikarya,
but this is not the case for GluN2A and GluN2B, while the neuropile compartment is less subject to modifications.
Thus, important variations in the pattern of distribution of the NMDA receptors subunits and PSD-95 represent a marker
in AD and by impairing the neuronal network, contribute to functional deterioration.
Keywords: Alzheimer, aging, cortex, synapses, neurons, PSD-95, GluN1, GluN2A, GluN2B.
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