Altmetric

Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases.

File Description SizeFormat 
Ruffmann C et al Neuropathol. Apply Neurobiol 2015.pdfAccepted version764.53 kBAdobe PDFView/Open
Title: Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases.
Authors: Ruffmann, C
Calboli, FC
Bravi, I
Gveric, D
Curry, LK
De Smith, A
Pavlou, S
Buxton, JL
Blakemore, AI
Takousis, P
Molloy, S
Piccini, P
Dexter, DT
Roncaroli, F
Gentleman, SM
Middleton, LT
Item Type: Journal Article
Abstract: © 2015 British Neuropathological SocietyAims: 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 Parkinsons disease with (PDD) and without (PDND) dementia. Methods: One hundred and twenty-one 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.
Issue Date: 3-Nov-2015
Date of Acceptance: 26-Oct-2015
URI: http://hdl.handle.net/10044/1/30027
DOI: https://dx.doi.org/10.1111/nan.12294
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/Funder: Parkinson's UK
Michael J Fox Foundation
West London Mental Health NHS Trust
Parkinson's UK
Funder's Grant Number: N/A
MJFF Research grant 2010 prog
n/a
J-1402
Keywords: 
Lewy bodies
Parkinson's disease
alpha-synuclein
dementia
neuropathology
Dementia
Lewy Bodies
Neuropathology
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Science
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons