Asparaginase-like protein 1 and human endogenous retroviruses link immune and gene dysregulation in dementia

Dementia is increasingly recognized as a condition characterized not only by neurodegeneration but also by significant immune alterations, with potential consequences for both humoral immunity and peripheral gene regulation. However, the relationship between these processes when targeting neuronal and retroviral antigens remains poorly understood. This study investigated immune responses to asparaginase-like protein 1 and human endogenous retroviruses in different types of dementia. Plasma and peripheral blood mononuclear cells were collected from patients with dementia. Antibody reactivity against asparaginase-like protein 1 and human endogenous retroviruses was assayed by enzyme-linked immunosorbent assay, while peripheral gene expression was quantified by qPCR. Group comparisons and correlation analyses were performed. Patients exhibited increased antibody responses against asparaginase-like protein 1 and human endogenous retroviruses despite reduced peripheral expression of the corresponding genes. Within patients, antibodies against asparaginase-like protein 1 were inversely correlated with its transcript levels, whereas antibody responses to human endogenous retroviruses correlated positively with residual gene expression. Immune and transcriptional measures targeting these molecules were interrelated, indicating shared immune pathways. For the first time, this study identifies a coordinated relationship between humoral immune responses and peripheral gene expression in the dementia such as AD, MCI and mixed Dementia offering a novel context for interpreting immune dysregulation and suggesting potential immune-based biomarkers linked to neurodegenerative processes.