Neuropathology of dementia in a large cohort of patients with Parkinson's disease

https://doi.org/10.1016/j.parkreldis.2013.05.010Get rights and content
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Abstract

The aim of our study was to establish the contribution of distinct pathological aggregates (cortical Lewy bodies (LB), neuronal tau-inclusions and β-amyloid plaque (Aβ) deposition) in dementia related to Parkinson's disease (PD) in a large autopsy cohort.

We studied the brains of 155 PD patients, 109 of whom were clinically demented. The total LB score, the Braak stages for neurofibrillary tangles (NFT) and the Thal phases for Aβ deposition were assessed in each case, according to previously published guidelines.

All the three lesion types were more abundant in the demented PD group, compared to the non-demented PD group, but neocortical LB pathology was the most important substrate of dementia. A significant correlation was found between the severity of Aβ phases, NFT stages and cortical LB scores. In a subgroup of severely demented PD patients, cortical tau burden was much higher than in the rest of the group. Extensive cortical NFTs associate unavoidably with dementia. Some patients remain cognitively intact despite high cortical LB score. In conclusion, our data strongly support a combining, yet distinct role of neocortical LBs and tau deposits.

Keywords

Dementia
Parkinson's disease
Neuropathology

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Editor's comment: Dementia develops frequently during the advanced phases of Parkinson's disease, and is termed Parkinson's disease dementia, or PDD. The pathological bases of this devastating complication are probably multifactorial and, currently, the objective of intensive investigations.

In this issue, Horvath et al. aim to dissect the role of four suspects in the development of PDD: the cortical alpha-synuclein pathology, tau pathology, beta-amyloid pathology, and cerebrovascular pathology, in a large series of brains from 155 PD patients (109 with PDD), collected at the Geneva University Brain Bank.

In a multivariate statistical analysis, the cortical alpha-synuclein pathology emerged as the most important substrate of dementia, with an odds ratio of 4.2. The cortical tau pathology burden was also an independent significant contributor, though with a lower odds ratio of 1.6. Thus, this study confirms the cortical alpha-synucleinopathy as the main pathological substrate of PDD, but also points to an important role for the tau pathology, particularly, perhaps, in the most severe stages of PDD. Furthermore, the study highlights that the burden of the cortical alpha-synuclein, tau, and beta-amyloid lesions appear to be inter-correlated; this fact, in keeping with data from experimental studies, suggests synergistic mechanisms in the aggregation of different proteins during the neurodegenerative diseases.

The study by Horvath et al., one of the largest of this kind, also reminds us of the richness and the great opportunities offered by the existing brain banks of patients with neurological disorders, of which the Geneva University Brain Bank is a prestigious representative.

Vincenzo Bonifati, Associate Editor, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands