Cognitive impairment in Parkinson's disease: amyloid plaques, neurofibrillary tangles, and neuropil threads in the cerebral cortex

Abstract

Sensitive silver methods for extracellular amyloid and intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) were employed to examine the cortical pathology in Parkinson's disease. In cases with cognitive impairment many plaque-like amyloid deposits were found in the cerebral cortex. Neuritic plaques were rare or absent. Neither the Ammon's horn nor the isocortex revealed a sufficiently large number of tangles to permit the diagnosis of a coexisting fully developed Alzheimer's disease. Large numbers of neurofibrillary tangles and neuropil threads were only found in layer Pre-alpha of the entorhinal cortex. This layer gives rise to major portions of the perforant tract, a pathway which serves as a link in the transmission of data from isocortical association areas to the hippocampal formation. During the course of Parkinson's disease the hippocampal formation is thus endangered to become disrupted from isocortical influences. It is concluded that the cognitive impairment shown by many individuals suffering from Parkinson's disease may partly be caused by cortical lesions.

Circulating Neurotoxic 5-HT2A Receptor Agonist Autoantibodies in Adult Type 2 Diabetes with Parkinson’s Disease

“…Diabetic depression autoantibody neurotoxicity could be prevented (in vitro) by co-incubating cells with specific antagonists of the 5-HT2A receptor [4]. Since the 5HT-2AR is concentrated on neurons in specific brain regions (anterior olfactory nucleus, transentorhinal cortex, substantia nigra, brainstem, hippocampus, medial prefrontal cortex) [5] affected by PD-or Alzheimers'type-neurodegeneration [6], in the present study we tested a hypothesis that circulating agonist, 5-HT2A receptor autoantibodies increase (and may contribute to pathophysiology) in older adult type 2 diabetes suffering with comorbid Parkinson's disease and/or dementia.…”

Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes

“…In summarizing his quantitative and comparative anatomical data, Stephan (1975) clearly demonstrated the progressive increase of CA1, subicular, and entorhinal volumes in man. Interestingly, these archicortical and periarchicortical structures exhibit characteristic pathological cha~!ges in a variety of neurodegenerative diseases, including Alzheimer's disease (Hirano and Zimmerman 1962;McLardy 1970;Hooper and Vogel 1976;Kemper 1978;Hyman et al 1984;Braak and Braak 1991), Parkinson's disease (Braak and Braak 1990), Pick's disease (Jakob 1979), and Huntington's chorea (Bauer et al 1991 ;Braak and Braak 1992 a, b;Heinsen et al 1992), diseases which exclusively afflict man. Cytoarchitectonic studies of schizophrenia, an additional disease confined to the human brain, point to specific circumscribed neurodevelopmental disturbances in the entorhinal region (Jakob and Beckmann 1986;Arnold et al 1991;Beckmann and Jakob 1991).…”

Idiopathic Parkinson's Disease, Vascular Risk Factors and Cognition: A Critical Review

“…However, there is evidence that cholesterol alters the degradation of amyloid precursor protein and shows an effect on amyloid fibril formation, which may play a role in the pathogenesis of AD (Sponne et al, 2004). Amyloid abnormalities were described in the brains of PD patients with cognitive impairment (Braak & Braak, 1990) as well as of PDD patients (Nobili et al, 2011). Therefore, HCL could be a VRF for cognitive impairment and PDD, via its possible contribution to amyloid aggregation.…”