Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease

Article type: Research Article

Authors: Miklossy, Judith^{a; b; *} | Khalili, Kamel^b | Gern, Lise^c | Ericson, Rebecca L.^d | Darekar, Pushpa^a | Bolle, Lorie^e | Hurlimann, Jean^a | Paster, Bruce J.^d

Affiliations: [a] University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland. and University of British Columbia, Department of Psychiatry, Kinsmen Laboratory of Neurological Research, Vancouver, B.C. V6T 1Z3, Canada | [b] Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA | [c] Institute of Zoology, University of Neuchâtel, 2007 Neuchâtel, Switzerland | [d] The Forsyth Institute, Department of Molecular Genetics, Boston 02115, Massachussets, USA | [e] Center of Blood Transfusion, University Medical School, CHUV, 1011, Lausanne, Switzerland

Correspondence: [*] Corresponding author: Judith Miklossy MD, University of British Columbia, Department of Psychiatry, Kinsmen Laboratory of Neurological Research, 2255 Wesbrook Mall, Vancouver, B.C., V6T 1Z3, Canada. Tel.: +1 604 822 7564; Fax: +1 604 822 7086; E-mail: [email protected].

Abstract: The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.

Keywords: Alzheimer's disease, amyloid, bacteria, Borrelia burgdorferi, chronic inflammation, lyme disease, spirochetes, syphilis

DOI: 10.3233/JAD-2004-6608

Journal: Journal of Alzheimer's Disease, vol. 6, no. 6, pp. 639-649, 2004