Herpes simplex virus type 1 in Alzheimer's disease: the enemy within.
Alzheimer's disease is a modern scourge and is likely to become increasingly so in the future, with increasing longevity. The disease has been investigated for over one hundred years yet its causes and that of the neuropathological characteristics seen in AD brain are still completely unknown. Evidence for a major causative role of a common virus, herpes simplex virus type 1 (HSV1), acting in combination with a genetic factor - the type 4 allele of the apolipoprotein gene, a known susceptibility factor - is presented here. The characteristics of the virus, some of which make it an especially likely candidate for this role, are described, as are the many precedents for the action of a genetic factor modulating outcome of infection. Various possible ways in which HSV1 might lead to development of AD, such as its up-regulation of various enzymes and in particular certain kinases, its effect on the cell cycle, on autophagy, and its inflammatory and oxidative effects are also discussed. It is concluded that there is strong evidence that the virus is indeed a major factor in AD and therefore there is a strong case for appropriate treatment, and possibly for prevention in the future.
Itzhaki
Ruth F
RF
Faculty of Life Science, The University of Manchester, Manchester, UK. ruth.itzhaki@manchester.ac.uk
Wozniak
Matthew A
MA
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology; D001057:Apolipoproteins E / Q000378:metabolism; D020803:Encephalitis, Herpes Simplex / Q000453:epidemiology / Q000821:virology; D006561:Herpes Simplex / Q000453:epidemiology* / Q000235:genetics / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins