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Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer’s disease

Lookup NU author(s): Dr Lauren WalkerORCiD, Professor Alan ThomasORCiD, Professor Johannes Attems



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s) 2024.Dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and Parkinson’s disease (PD) collectively known as Lewy body diseases (LBDs) are neuropathologically characterised by α-synuclein deposits (Lewy bodies and Lewy neurites). However, LBDs also exhibit pathology associated with Alzheimer’s disease (AD) (i.e. hyperphosphorylated tau and amyloid β (Aβ). Aβ can be deposited in the walls of blood vessels in the brains of individuals with AD, termed cerebral amyloid angiopathy (CAA). The aim of this study was to investigate the type and distribution of CAA in DLB, PDD, and PD and determine if this differs from AD. CAA type, severity, and topographical distribution was assessed in 94 AD, 30 DLB, 17 PDD, and 11 PD cases, and APOE genotype evaluated in a subset of cases where available. 96.3% AD cases, 70% DLB cases and 82.4% PDD cases exhibited CAA (type 1 or type 2). However only 45.5% PD cases had CAA. Type 1 CAA accounted for 37.2% of AD cases, 10% of DLB cases, and 5.9% of PDD cases, and was not observed in PD cases. There was a hierarchical topographical distribution in regions affected by CAA where AD and DLB displayed the same distribution pattern that differed from PDD and PD. APOE ε4 was associated with severity of CAA in AD cases. Topographical patterns and severity of CAA in DLB more closely resembled AD rather than PDD, and as type 1 CAA is associated with clinical dementia in AD, further investigations are warranted into whether the increased presence of type 1 CAA in DLB compared to PDD are related to the onset of cognitive symptoms and is a distinguishing factor between LBDs. Possible alignment of the the topographical distribution of CAA and microbleeds in DLB warrants further investigation. CAA in DLB more closely resembles AD rather than PDD or PD, and should be taken into consideration when stratifying patients for clinical trials or designing disease modifying therapies.

Publication metadata

Author(s): Walker L, Simpson H, Thomas AJ, Attems J

Publication type: Article

Publication status: Published

Journal: Acta Neuropathologica Communications

Year: 2024

Volume: 12

Issue: 1

Online publication date: 15/02/2024

Acceptance date: 17/12/2023

Date deposited: 05/03/2024

ISSN (electronic): 2051-5960

Publisher: BioMed Central Ltd


DOI: 10.1186/s40478-023-01714-7

PubMed id: 38360761


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Funder referenceFunder name
Alzheimer’s Research UK
Alzheimer’s Society
Brains for Dementia research
Medical Research Council