Reduction in post-synaptic scaffolding PSD-95 and SAP-102 protein levels in the Alzheimer inferior temporal cortex is correlated with disease pathology.
N-methyl-D-aspartate (NMDA) receptor-evoked excitotoxicity contributes to region-specific loss of glutamatergic synapses responsible for cognitive decline in Alzheimer's disease (AD). Here, the post-synaptic scaffold proteins PSD-95 and SAP-102, which regulate NMDA receptor synaptic activity and expression, were investigated in human AD autopsy brain tissue. Using absolute quantification real-time PCR, we detected reduced expression of synaptophysin in both the pathologically susceptible inferior temporal cortex and hippocampus, consistent with previous reports. PSD-95 and SAP-102 mRNA was reduced, albeit not significantly. Proteins were precisely quantified against recombinant truncated protein standards. No differences were observed for proteins in AD spared occipital cortex between AD cases and controls. PSD-95 and SAP-102 protein expression was markedly reduced in the AD inferior temporal cortex. Both mRNA and protein levels were reduced according to disease severity. SAP102 protein levels were significantly reduced in AD subjects carrying a copy of the APOEε4 allele. This is the first study to investigate SAP-102 in the aging human brain and suggest a possible mechanism for NMDA receptor expression aberrations in AD.
Proctor
Dustin T
DT
School of Chemistry and Molecular Bioscience, University of Queensland, Brisbane, Australia.
Coulson
Elizabeth J
EJ
Dodd
Peter R
PR
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D000076122:Disks Large Homolog 4 Protein; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C116869:DLG3 protein, human; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D016708:Synaptophysin; D014157:Transcription Factors