Our results further suggest that the SYK up-regulation observed in the brains of individuals with AD contributes to defective autophagic clearance leading to the accumulation of pathogenic Tau species.
Our previous studies have shown that Nilvadipine inhibits spleen tyrosine kinase (Syk), is effective at reducing inflammation, tau hyperphosphorylation, and amyloid production, and it has recently been investigated in a European Phase III clinical trial for Alzheimer's disease (AD).
It has been proposed that increased immunoreactivity for double-phosphorylated Syk in hippocampal neurons of Alzheimer's disease cases indicates a not yet defined neurodegenerative process.
Importantly, human AD brain sections show both pathological Syk activation in DNs around Aβ deposits and in neurons immunopositive for pathological tau species recapitulating the data obtained in transgenic mouse models of AD.
We find that aged microglial cells are more susceptible to the formation of SGs; and SGs containing SYK and phosphotyrosine are prevalent in the brains of patients with severe Alzheimer's disease.