Introduction: Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent lines of evidence. We explored this association by comparing the frequencies of viral species identified in a large sample of AD cases and controls.
Methods: DNA sequence reads that did not align to the human genome in sequences were mapped to viral reference sequences, quantified, and then were tested for association with AD in whole exome sequences (WES) and whole genome sequences (WGS) datasets.
Results: Several viruses were significant predictors of AD according to the machine learning classifiers. Subsequent regression analyses showed that herpes simplex type 1 (HSV-1) (odds ratio [OR] = 3.71, p = 8.03 × 10-4) and human papillomavirus 71 (HPV-71; OR = 3.56, p = 0.02), were significantly associated with AD after Bonferroni correction. The phylogenetic-related cluster of Herpesviridae was significantly associated with AD in several strata of the data (p < 0.01).
Discussion: Our results support the hypothesis that viral infection, especially HSV-1, is associated with AD risk.
Keywords: Alzheimer's disease; Alzheimer's disease sequencing project; antiviral agents; herpes simplex; human papillomavirus; torque teno viruses; whole exome sequencing; whole genome sequencing.
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.