The PILRA G78R Variant Correlates with Higher HSV-1-Specific IgG Titers in Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive performance; Mild Cognitive Impairment (MCI) is instead an objective decline in cognitive performance that does not reach pathology. Paired immunoglobulin-like type 2 receptor alpha (PILRA) is a cell surface inhibitory receptor that was recently suggested to be involved in AD pathogenesis. In particular, the arginine-to-glycine substitution in position 78 (R78, rs1859788) was shown to be protective against AD. Herpes simplex virus type 1 (HSV-1) infection is suspected as well to be involved in AD. Interestingly, HSV-1 uses PILRA to infect cells, and HSV-1 infects more efficiently PIRLA G78 compared to R78 macrophages. We analyzed PILRA rs1859788 polymorphism and HSV-1 humoral immune responses in AD ( n = 61) and MCI patients ( n = 48), and in sex and age matched healthy controls (HC; n = 57). The rs1859788 PILRA genotype distribution was similar among AD, MCI and HC; HSV-1 antibody (Ab) titers were increased in AD and MCI compared to HC ( p