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

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 26 bp 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 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 VAMP2 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. 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.

Non-coding variants in VAMP2 and SNAP25 affect gene expression: potential implications in migraine susceptibility

“…Several studies indicated that abnormal expression, risk genetic variants, or dysfunction of SNARE proteins are present in various neurological diseases, possibly contributing to abnormal neurotransmission and synaptic dysfunction [ 18 ]. In line with our findings, VAMP2 expression was found to be reduced in animal models or patients' brain tissues of Parkinson [ 26 ], epilepsy [ 27 ], and dementia [ 28 ]. As proposed in vascular dementia, VAMP2 _rs1150 risk allele may have a potential role in synaptic decline and vascular alterations [ 28 ].…”

“…In line with our findings, VAMP2 expression was found to be reduced in animal models or patients' brain tissues of Parkinson [ 26 ], epilepsy [ 27 ], and dementia [ 28 ]. As proposed in vascular dementia, VAMP2 _rs1150 risk allele may have a potential role in synaptic decline and vascular alterations [ 28 ]. In these same studies, SNAP25 and STX1A expression was decreased, in opposition to our results of the SNAP25 _rs2327264 risk allele.…”

VAMP2 Gene-Related Neurodevelopmental Disorder: A Differential Diagnosis for Rett/Angelman-Type Spectrum of Disorders

“…VAMP2 is encoded by the VAMP2 gene, which is located on chromosome 17p13.1 and consists of six exons [Costa et al, 2022]. Previous in vitro studies have demonstrated that pathogenic variants affecting its SNARE motif (sequence of the protein with a tendency to form coiled coils [Rizo and Rosenmund, 2008]) can interfere with liposomal fusion and promotion of plasma membrane "zippering" via Munc18 [Hernandez et al, 2012;Shen et al, 2015].…”