The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer's Disease: Implications for Treatment

Alzheimer's disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), beta-amyloid (A beta), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at A beta deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in A beta and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of beta-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.

Automated summary

SV2A expression down-regulation in AD may be related to APP, Aβ, and Tau proteins; SV2A deficiency may lead to an increase in Aβ and Tau hyperphosphorylation, while overexpression may be associated with down-regulation of APP cleaving enzyme and apolipoprotein E genes; evidence suggests the phosphatidylinositol 3-kinase signaling pathway may mediate SV2A regulation influencing AD incidence and development.