APP, APOE, complement receptor 1, clusterin and PICALM and their involvement in the herpes simplex life cycle.
Neurosci Lett. 2010 Oct 11;483(2):96-100.
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These are not the only Alzheimer's disease-related genes that are implicated in the viral life cycle. Others are catalogued at Polygenic Signaling Pathways, and there is also a database of Herpes simplex host viral interactions.
It is worth pointing out that Herpes simplex infection in mice produces entorhinal and hippocampal cell loss, cerebral shrinkage, and memory deficits (Armien et al., 2010). The lesions are not exactly those seen in Alzheimer's disease, (nor are those from the various APP transgenic models) but they show that viral infection can produce many of its features. Ruth Itzhaki's group has also shown that viral infection produces β amyloid deposition and increases tau phosphorylation.
Two years ago, a retrospective analysis showed that HSV-1 seropositivity, of the type indicating viral reactivation, was a reliable predictor of the subsequent development of Alzheimer's disease (Letenneur et al., 2008).
The importance here is that viral infection precedes the development of Alzheimer's disease-like features. Attacking the virus may prevent, rather than cure. It is surely time to consider regular viral screening in the aging population, and clinical trials with antiviral agents.
Armien AG, Hu S, Little MR, Robinson N, Lokensgard JR, Low WC, Cheeran MC.
Chronic cortical and subcortical pathology with associated neurological deficits ensuing experimental herpes encephalitis.
Brain Pathol. 2010 Jul;20(4):738-50.
Wozniak MA, Frost AL, Itzhaki RF.
Alzheimer's disease-specific tau phosphorylation is induced by herpes simplex virus type 1.
J Alzheimers Dis. 2009;16(2):341-50.
Wozniak MA, Itzhaki RF, Shipley SJ, Dobson CB.
Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation.
Neurosci Lett. 2007 Dec 18;429(2-3):95-100.
Shipley SJ, Parkin ET, Itzhaki RF, Dobson CB.
Herpes simplex virus interferes with amyloid precursor protein processing.
BMC Microbiol. 2005;5:48.
Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Orgogozo JM, Gauthier S, Dartigues JF.
Seropositivity to herpes simplex virus antibodies and risk of Alzheimer's disease: a population-based cohort study.
PLoS One. 2008;3(11):e3637.
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