title: Challenges and directions for the pathogen hypothesis of Alzheimer's disease.
abstract: This paper critically reviews the possibility that infiltration of the brain by pathogens (e.g. Herpes simplex virus type 1 (HSV1) or Chlamydophila pneumoniae (Cp)) acts as a trigger or co-factor for Alzheimer's disease (AD). The evidence currently available is limited and in some cases inconsistent, but it does justify the need for more vigorous investigation of this hypothesis. An issue of particular concern is the paucity of experimental evidence showing that pathogens can elicit the neuropathological changes and cognitive deficits that characterise AD. Other weaknesses include a failure to obtain independent confirmation of Cp in AD brains, and a lack of evidence for HSV1 proteins or intact virions in AD brain tissue. Future avenues of investigation that might prove fruitful include epidemiological investigations of the incidence of AD in individuals who are either immunosuppressed or have received chronic antiviral or antibiotic therapy. There is also a need to consider systemic infections as potential contributors to the pathogenesis of AD.
authors.affiliation: Department of Psychology, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Vic. 3800, Australia. stephen.robinson@med.monash.edu.au
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Robinson
authors.forename: Curtis
authors.initials: C
authors.lastname: Dobson
authors.forename: Joseph
authors.initials: J
authors.lastname: Lyons
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000382:microbiology / Q000821:virology; D000818:Animals; D001927:Brain Diseases / Q000150:complications* / Q000382:microbiology / Q000821:virology; D002690:Chlamydia Infections / Q000150:complications; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D020803:Encephalitis, Herpes Simplex / Q000150:complications; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D012307:Risk Factors