Glycosylation States of Pre- and Post-synaptic Markers of 5-HT Neurons Differ With Sex and 5-HTTLPR Genotype in Cortical Autopsy Samples
Abstract
The serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is thought to alter 5-HT signaling and contribute to behavioral and cognitive phenotypes in depression as well as Alzheimer disease (AD). We explored how well the short (S) and long (L) alleles of the 5-HTTLPR align with serotoninergic indices in 60 autopsied cortical samples from early-onset AD/EOAD and late-onset AD/LOAD donors, and age- and sex-matched controls. Stratifying data by either diagnosis-by-genotype or by sex-by-genotype revealed that the donor's 5-HTTLPR genotype, i.e., L/L, S/L, or S/S, did not affect 5-HTT mRNA or protein expression. However, the glycosylation of 5-HTT was significantly higher in control female (vs. male) samples and tended to decrease in female EOAD/LOAD samples, but remained unaltered in male LOAD samples. Glycosylated forms of the vesicular monoamine transporter (VMAT2) were lower in both male and female AD samples, while a sex-by-genotype stratification revealed a loss of VMAT2 glycosylation specifically in females with an L/L genotype. VMAT2 and 5-HTT glycosylation were correlated in male samples and inversely correlated in female samples in both stratification models. The S/S genotype a...Continue Reading
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