AUTHOR=Costa Andrea Saul , Ferri Evelyn , Guerini Franca Rosa , Rossi Paolo Dionigi , Arosio Beatrice , Clerici Mario 

TITLE=VAMP2 Expression and Genotype Are Possible Discriminators in Different Forms of Dementia

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.858162

DOI=10.3389/fnagi.2022.858162

ISSN=1663-4365

ABSTRACT=Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer’s Disease (AD). The 26bp intergenic polymorphism of VAMP2, a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated ApoE4 and VAMP2 26bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as VAMP2 gene expression in a subset of 73 AD, 122 MD, 140 CT and 103 MCI. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time. VAMP2 mRNA was higher in MD compared to AD (p=0.0013) and CT (p=0.0017), and in MCI-MD compared to MCI-AD (p<0.001) after correcting for age, gender, MMSE and ApoE4+/- covariates (pc=0.004). A higher VAMP2 expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (p=0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (pc=0.036). These results suggest that VAMP2 mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients.