title: Infiltration of the brain by pathogens causes Alzheimer's disease.
abstract: Despite very numerous studies on Alzheimer's disease (AD), especially on amyloid plaques and neurofibrillary tangles, little information has been obtained thus on the causes of the disease. Evidence is described here that implicates firstly herpes simplex virus type 1 (HSV1) as a strong risk factor when it is present in brain of carriers of the type 4 allele of the gene for apolipoprotein E (APOE-4). Indirect support comes from studies indicating the role of APOE in several diverse diseases of known pathogen cause. A second putative risk factor is the bacterium, Chlamydia pneumoniae. This pathogen has been identified and localized in AD brain. Current studies aimed at "proof of principle" address the entry of the organism into the CNS, the neuroinflammatory response to the organism, and the role that the organism plays in triggering AD pathology. An infection-based animal model demonstrates that following intranasal inoculation of BALB/c mice with C. pneumoniae, amyloid plaques/deposits consistent with those observed in the AD brain develop, thus implicating this infection in the etiology of AD.
authors.affiliation: Department of Optometry and Neuroscience, University of Manchester Institute of Science and Technology (UMIST), Manchester M60 1QD, UK. Ruth.Itzhaki@umist.ac.uk
authors.forename: R F
authors.initials: RF
authors.lastname: Itzhaki
authors.forename: M A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: D M
authors.initials: DM
authors.lastname: Appelt
authors.forename: B J
authors.initials: BJ
authors.lastname: Balin
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000382:microbiology / Q000821:virology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D017848:Blood-Borne Pathogens; D001927:Brain Diseases / Q000150:complications* / Q000382:microbiology / Q000821:virology; D023521:Chlamydophila Infections / Q000150:complications; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity; D004195:Disease Models, Animal; D019317:Evidence-Based Medicine; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D016874:Neurofibrillary Tangles / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E