Herpes simplex virus type 1 (HSV-1) is latent in the nervous system of most humans. Ball [Can J Neurol Sci 9 (1982) 303] first suggested the hypothesis that HSV-1 could be involved in the pathogenesis of Alzheimer's Disease (AD) by noting that regions of the brain particularly and earliest affected in AD were the same as those most damaged during HSV encephalitis. Data from Itzhaki's research suggests that HSV-1 in the brain and the carriage of an apolipoprotein E allele 4 (ApoE e4) together confer risk for AD [J Pathol 97 (2002) 395], [Mol Chem Neuropathol 28 (1996) 135], [Alzheimer's Rep 1 (1998) 173], [Biochem Soc Trans 26 (1998) 273]. Of the two other studies based on Itzhaki's findings, one showed similar results [Lancet 349 (1997) 1102], and the other showed a similar trend [Lancet 351 (1998) 1330], [Lancet 352 (1998) 1312]. To further examine the role of HSV-1 in the etiology of AD, we have formulated a Neuroinvasive Score that quantifies the presence and viral load of HSV-1 in eight brain regions. These regions are: entorhinal cortex, hippocampus, pons, cerebellum, and neocortex (temporal, parietal, occipital, and frontal). We hypothesize that the Neuroinvasive Score that encompasses the presence, amount, and extent of HSV-1 spreading (neuroinvasiveness), will correlate with the genetic risk factor, ApoE e4, in the assessment of autopsy samples from AD patients. If the neuroinvasive score can be directly correlated to the different stages of AD (mild, moderate, severe), this will strengthen the hypothesis that HSV-1 is involved in AD and that ApoE e4 also confers risk for the development and progression of AD.