Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques. Export

@article{citeulike:3753810, abstract = {The brains of Alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-\ϵ4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer's disease brains, 90\% of the plaques contained the viral DNA and 72\% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80\% of plaques contained herpes simplex virus type 1 DNA but only 24\% of the viral DNA was plaque-associated (p \< 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of beta-amyloid (Abeta), so that less of the viral DNA is seen to be associated with Abeta in the brain. Our present data, together with our finding of Abeta accumulation in herpes simplex virus type 1-infected cells and mouse brain, suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer's disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it. Copyright {\\\\\\\\copyright} 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley \& Sons, Ltd.}, address = {Faculty of Life Sciences, University of Manchester, UK; Department of Medicine, Manchester Royal Infirmary, UK}, author = {Wozniak, M. A. and Mee, A. P. and Itzhaki, R. F.}, citeulike-article-id = {3753810}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/path.2449}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18973185}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18973185}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/121411445/ABSTRACT}, citeulike-linkout-4 = {http://dx.doi.org/http://dx.doi.org/10.1002/path.2449}, citeulike-linkout-5 = {http://dx.doi.org/10.1002/path.2449}, doi = {10.1002/path.2449}, issn = {1096-9896}, journal = {The Journal of pathology}, keywords = {e-slr, epidemiology}, month = {January}, number = {1}, pages = {131--138}, posted-at = {2008-12-07 23:24:45}, priority = {2}, title = {Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques.}, url = {http://dx.doi.org/10.1002/path.2449}, volume = {217}, year = {2009} }

TY - JOUR ID - citeulike:3753810 L3 - citeulike-article-id:3753810 N2 - The brains of Alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-ϵ4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer's disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80% of plaques contained herpes simplex virus type 1 DNA but only 24% of the viral DNA was plaque-associated (p < 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of beta-amyloid (Abeta), so that less of the viral DNA is seen to be associated with Abeta in the brain. Our present data, together with our finding of Abeta accumulation in herpes simplex virus type 1-infected cells and mouse brain, suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer's disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it. Copyright {\\\\\\\\copyright} 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. IS - 1 JF - The Journal of pathology SN - 1096-9896 AD - Faculty of Life Sciences, University of Manchester, UK; Department of Medicine, Manchester Royal Infirmary, UK EP - 138 TI - Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques. VL - 217 SP - 131 KW - e-slr KW - epidemiology AU - Wozniak, MA AU - Mee, AP AU - Itzhaki, RF PY - 2009/01// UR - http://dx.doi.org/10.1002/path.2449 ER -