Postencephalitic Parkinson's disease, amyotrophic lateral sclerosis on Guam and influenza revisited: focusing on neurofibrillary tangles and the trail of tau.

Circumstantial evidence links neuropathological changes in postencephalitic Parkinson's disease and amyotrophic lateral sclerosis on Guam to the 1918 influenza pandemic. Postencephalitic Parkinson's disease and amyotrophic lateral sclerosis have neuronal neurofibrillary tangles that anatomically correlate with clinical signs and symptoms. Occurrences of the disorders peaked in the early 1950s and are now disappearing. Neurovirulent influenza associated with the lethal 1918 pandemic is suggested as the etiology of both diseases. Permissive tissue antigens are considered an important contributing factor. Neurofibrillary tangles also correlate with signs and symptoms in Alzheimer's disease. Oxidative stress may be the pathological process that induces neurofibrillary tangles. Tangles contain abnormally phosphorylated tau. In Alzheimer's disease, tau is present in cerebrospinal fluid and is deposited in corpora amylacea, demonstrating the direction of cerebrospinal fluid flow.