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=14

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