Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases.
File(s)
Author(s)
Type
Journal Article
Abstract
AIMS: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. METHODS: 121 cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. RESULTS: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, p<0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (p=0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (p=0.02), particularly in the neocortical frontal, parietal, and temporal regions. CONCLUSIONS: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele. This article is protected by copyright. All rights reserved.
Date Issued
2015-11-03
Date Acceptance
2015-10-26
Citation
Neuropathology and Applied Neurobiology, 2015, 42 (5), pp.436-450
ISSN
1365-2990
Publisher
Wiley
Start Page
436
End Page
450
Journal / Book Title
Neuropathology and Applied Neurobiology
Volume
42
Issue
5
Copyright Statement
This is the peer reviewed version of the following article: C. Ruffmann, F. C. F. Calboli, I. Bravi, D. Gveric, L. K. Curry, A. de Smith, S. Pavlou, J. L Buxton, A. I. F. Blakemore, P. Takousis, S. Molloy, P. Piccini, D. T. Dexter, F. Roncaroli, S. M. Gentleman, L. T. Middleton (2015) Neuropathology and Applied Neurobiology Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases, which has been published in final form at https://dx.doi.org/10.1111/nan.12294. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Sponsor
Parkinson's UK
Michael J Fox Foundation
West London Mental Health NHS Trust
Parkinson's UK
Grant Number
N/A
MJFF Research grant 2010 prog
n/a
J-1402
Subjects
Aβ
Dementia
Lewy Bodies
Neuropathology
Parkinson's disease
alpha-synuclein
Publication Status
Published