Francis Mawanda, Robert Wallace

Late-onset Alzheimer's disease (AD) is the most prevalent cause of dementia among older adults, yet more than a century of research has not determined why this disease develops. One prevailing hypothesis is that late-onset AD is caused by infectious pathogens, an idea widely studied in both humans and experimental animal models. This review examines the infectious AD etiology hypothesis and summarizes existing evidence associating infectious agents with AD in humans. The various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD are considered, as is the concordance between putative infectious agents and the epidemiology of AD. We searched the PubMed, Web of Science, and EBSCO databases for research articles pertaining to infections and AD and systematically reviewed the evidence linking specific infectious pathogens to AD. The evidence compiled from the literature linking AD to an infectious cause is inconclusive, but the amount of evidence suggestive of an association is too substantial to ignore. Epidemiologic, clinical, and basic science studies that could improve on current understanding of the associations between AD and infections and possibly uncover ways to control this highly prevalent and debilitating disease are suggested.