Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: implications for Alzheimer disease pathogenesis.
Though silent and likely not functionally relevant, rs13180 is in complete LD with rs2656070 (D' > 0.999), creating an IREB2-haplotype that is significantly associated with AD.
MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity. Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease.
One marker, rs498055, located in a gene homologous to RPS3A (LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples.
The dysregulation of cytokine production observed in AD patients may partially be explained by a significant reduction in the expression of RACK-1, a protein crucial for integration of signaling pathways with different physiological functions, such as cytokine production.
However, the up-regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.
Our results indicate that PGE2 signaling via the EP2 receptor promotes age-dependent oxidative damage and increased Abeta peptide burden in this model of AD, possibly via effects on BACE1 activity.