Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques
|MA Wozniak 1, AP Mee 2 a, RF Itzhaki 1 *|
|1Faculty of Life Sciences, University of Manchester, UK|
2Department of Medicine, Manchester Royal Infirmary, UK
|email: RF Itzhaki (ruth.itzhaki@manchester. ac.uk)|
*Correspondence to RF Itzhaki, Faculty of Life Sciences (North Campus), Moffat Building, University of Manchester, PO Box 88, Manchester M60 1QD, UK.
aCurrent address: Directorate of Laboratory Medicine, CMMC, Oxford Road, Manchester M13 9PL, UKNo conflicts of interest were declared.
|brain • Alzheimer's disease • herpes simplex encephalitis • herpes simplex virus type 1 • amyloid plaques • apolipoprotein E • in situ polymerase chain reaction • thioflavin S staining • immunohistochemistry|
|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-4), and that -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 < src="http://www3.interscience.wiley.com/giflibrary/12/beta.gif" align="absbottom" border="0">-amyloid (A), so that less of the viral DNA is seen to be associated with A in the brain. Our present data, together with our finding of A 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 © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.|
Received: 24 June 2008; Revised: 6 August 2008; Accepted: 5 September 2008
|Digital Object Identifier (DOI)|
10.1002/path.2449 About DOI
Article on this discovery from The Washington Post:
Cold Sore Virus Linked to Alzheimer's
People who develop cold sores may be at increased risk for Alzheimer's disease, according to British researchers who said the herpes virus that causes cold sores is a major cause of the brain protein plaques associated with Alzheimer's.
The University of Manchester team found DNA evidence of the herpes simplex virus (HSV) type 1 in 90 percent of plaques in Alzheimer's patients'brains, BBC News reported. The findings were published in the Journal of Pathology.
"We suggest that HSV1 enters the brain in the elderly as their immune systems decline and then establishes a dormant infection from which it is repeatedly activated by events such as stress, immunosuppression, and various infections," said Professor Ruth Itzhaki. This causes damage to brain cells, which die and disintegrate, releasing the proteins that form the plaques that cause Alzheimer's, the study suggested.
The potential good news in this study is that antiviral drugs used to treat cold sores may also prevent dementia. Itzhaki and colleagues plan to test that theory, BBC News reported.