Issue title: Chronic Inflammation and Amyloidogenesis in Alzheimer's Disease: The Emerging Role of Infection
Guest editors: Judith Miklossyx and Ralph N. Martinsy
Article type: Research Article
Authors: Miklossy, Judith; *
Affiliations: University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada | [x] The University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada | [y] Sir James McCusker Alzheimer's Disease Research Unit, University of Western Australia, Hollywood Private Hospital, 115 Monash Avenue, Nedlands, Perth, WA 6009, Australia
Correspondence:
[*]
Corresponding author: Judith Miklossy, MD, PhD, University of British Columbia, Kinsmen Laboratory of Neurological Research, 2255 Wesbrook Mall, Room 3N6, Vancouver, BC, Canada. Tel.: +1 604 822 7564; +4179372 9663; E-mail: [email protected].
Note: [1] Grant supports: Societe Academique Vaudoise, Switzerland; University Institute of Histology and Embryology, University of Fribourg, Switzerland, Pacific Alzheimer’s Foundation, The University of British Columbia, Vancouver, Canada.
Abstract: Alzheimer's disease (AD) is associated with dementia, brain atrophy and the aggregation and accumulation of a cortical amyloid-β peptide (Aβ). Chronic bacterial infections are frequently associated with amyloid deposition. It had been known from a century that the spirochete Treponema pallidum can cause dementia in the atrophic form of general paresis. It is noteworthy that the pathological hallmarks of this atrophic form are similar to those of AD. Recent observations showed that bacteria, including spirochetes contain amyloidogenic proteins and also that Aβ deposition and tau phosphorylation can be induced in or in vivo following exposure to bacteria or LPS. Bacteria or their poorly degradable debris are powerful inflammatory cytokine inducers, activate complement, affect vascular permeability, generate nitric oxide and free radicals, induce apoptosis and are amyloidogenic. All these processes are involved in the pathogenesis of AD. Old and new observations, reviewed here, indicate that to consider the possibility that bacteria, including several types of spirochetes highly prevalent in the population at large or their persisting debris may initiate cascade of events leading to chronic inflammation and amyloid deposition in AD is important, as appropriate antibacterial and antiinflammatory therapy would be available to prevent dementia.
Keywords: Alzheimer's disease, amyloid-β, bacteria, borrelia burgdorferi, chronic inflammation, dementia, general paresis, intestinal spirochetes, LPS, lyme neuroborreliosis, neurospirochetosis, oral spirochetes, spirochetes, syphilis, treponema pallidum
DOI: 10.3233/JAD-2008-13404
Journal: Journal of Alzheimer's Disease, vol. 13, no. 4, pp. 381-391, 2008
