Parkinson's disease dementia – A diminished role for the Lewy body

Abstract

The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n = 16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an “innocent-bystander”. The entire role of the LB in PD dementia is again brought into question.

Parkinson's disease, cortical dysfunction, and alpha‐synuclein

“…Phosphorylation is an example of post‐translational modification and has been proposed to be associated with toxicity and α‐synuclein aggregation. However, the ratio of phosphorylated to total α‐synuclein was not altered in our PD+myoclonus cases, and other investigators have evidence that phosphorylation is not directly responsible for α‐synuclein toxicity 31–33. Membrane disruption of α‐synuclein can alter the electrical properties of neurons, causing abnormal neuron firing 21, 34–38.…”

Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway

“…The density of both limbic LBs and neuritic plaques correlated well with the severity of the dementia,327 although hippocampal atrophy and cell loss are not necessarily involved in the memory impairment in PD 328. Increasing cognitive decline with increasing pathologic LB stages from 3 to 6 secondary to progression of αSyn pathology208 was not confirmed by others 211, 309, 327, 329–331. PD patients without dementia may have AD pathology largely restricted to the limbic system (neuritic Braak stage < 4), whereas patients with PDD often have severe AD lesions, with or without neocortical atrophy.…”

Vulnerable Neural Systems and the Borderland of Brain Aging and Neurodegeneration

“…However, these pathological processes fail to account for many cases of PD-associated cognitive decline (Libow et al, 2009). In fact, the essential neurochemical disturbances associated with PD provide a compelling explanation for some forms of age-related cognitive decline.…”