The Role of Chronic Infection in Alzheimer’s Disease: Instigators, Co-conspirators, or Bystanders?

Purpose of Review: Herein, we provide a critical review of the clinical and translational research examining the relationship between viral and bacterial pathogens and Alzheimer’s disease. In addition, we provide an overview of the biological pathways through which chronic infection may contribute to Alzheimer’s disease. Recent Findings: Dementia due to Alzheimer’s disease is a leading cause of disability among older adults in developed countries, yet knowledge of the causative factors that promote Alzheimer’s disease pathogenesis remains incomplete. Over the past several decades, numerous studies have demonstrated an association of chronic viral and bacterial infection with Alzheimer’s disease. Implicated infectious agents include numerous herpesviruses (HSV-1, HHV-6, HHV-7) and various gastric, enteric, and oral bacterial species, as well as Chlamydia pneumonia and multiple spirochetes. Summary: Evidence supports the association between multiple pathogens and Alzheimer’s disease risk. Whether these pathogens play a causal role in Alzheimer’s pathophysiology remains an open question. We propose that the host immune response to active or latent infection in the periphery or in the brain triggers or accelerates the Alzheimer’s disease processes, including the accumulation of amyloid-ß and pathogenic tau, and neuroinflammation. While recent research suggests that such theories are plausible, additional longitudinal studies linking microorganisms to Aß and phospho-tau development, neuroinflammation, and clinically defined Alzheimer’s dementia are needed.