Dementia in Parkinson's disease: biochemical evidence for cortical involvement using the immunodetection of abnormal Tau proteins.

In order to elucidate the neurochemical basis of the dementia of Parkinson's disease, we compared samples of cerebral cortex from 24 nondemented parkinsonian patients and parkinsonian patients with various degrees of dementia, with those from patients with Alzheimer's disease and control subjects, using a quantitative Western blot analysis. An anti-paired helical filaments antibody was used for the immunodetection of the abnormally phosphorylated Tau proteins 55, 64, and 69, which are known to be specific and reliable biochemical markers of Alzheimer-type neurofibrillary degeneration. The frequency and intensity of immunodetection of the abnormal Tau triplet were higher in the demented parkinsonian subgroups than in the nondemented parkinsonian subgroup in the prefrontal area, temporal cortex, and entorhinal cortex but not in either the occipital or the cingular cortex. A quantification of abnormal Tau triplet by densitometry showed that unlike the results obtained in Alzheimer patients, the intensity of lesions in the cerebral cortex of the most demented parkinsonian patients was more severe in the prefrontal area versus the temporal area. This study (1) gives biochemical evidence for Alzheimer-type changes in the cortex of demented parkinsonian patients and (2) suggests that lesions of the prefrontal cortex may significantly contribute to the occurrence of cognitive changes at least in some patients with Parkinson's disease.