Dementia in Parkinson's disease: Biochemical evidence for cortical involvement using the immunodetection of abnormal tau proteins

Abstract

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.

Senile Dementia of Lewy Body Type and Alzheimer Type Are Biochemically Distinct in Terms of Paired Helical Filaments and Hyperphosphorylated Tau Protein (Part 2 of 2)

“…In this study, the diffuse plaque was the pre dominant type found in PD cases as has been reported for the P-amyloid deposits in DLBD [24], Diffuse plaques might contribute less to the SDS-insoluble species of p/A4 protein that we have measured biochemically but this is the species regarded as having particular neurotoxicity. In a recent study of demented and non-demented PD cases, it was reported that abnormal phosphorylation of tau pro tein was evident in prefrontal, temporal and entorhinal cortices and, to a lesser extent, in cingulate cortex (10-20% of the level in AD) of the demented PD cases [76]. In this study, we found no evidence that protease-resistant PHF content or levels of hyperphosphorylated tau protein in cingulate cortex could distinguish the 7 cases of PD with dementia from those without.…”

Effects of Transient Focal Inactivation of the Basal Ganglia in Parkinsonian Primates

“…Conceivably, the compensatory mechanisms that come into play after lesioning are different between these circuits or perhaps many of the behavioral abnormalities in parkinsonism result from other mechanisms, such as cortical neuronal degeneration (Vermersch et al, 1993) or nondopaminergic neurotransmitter deficits (Bedard et al, 1998(Bedard et al, , 1999, which are only further aggravated by subcortical lesioning. Regardless of the mechanisms involved, the more compressed anatomical architecture of the STN, relative to GPi, could impart a higher associated risk for cognitive side effects from stimulation or inadvertent extension of lesions into nonmotor regions.…”

Regional Brain Atrophy in Idiopathic Parkinson's Disease and Diffuse Lewy Body Disease

“…The late-onset PD cases had significant cortical plaque pathology compared with controls and middle-age-onset cases but were with out cortical neuronal pathology. However, significant dis ruption of the neuropil is present in the frontal lobes of patients with PD dementia in the form of an accumula tion of abnormal tau and neurofilament proteins [38,39]. This may represent the disruption of subcortical afferents.…”