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Open Access 01-12-2019 | Parkinson's Disease | Research

Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson’s disease with cognitive decline

Authors: Alan King Lun Liu, Tsz Wing Chau, Ernest Junwei Lim, Idil Ahmed, Raymond Chuen-Chung Chang, Michail E. Kalaitzakis, Manuel B. Graeber, Steve M. Gentleman, Ronald K. B. Pearce

Published in: Acta Neuropathologica Communications | Issue 1/2019

Abstract

Although the precise neuropathological substrates of cognitive decline in Parkinson’s disease (PD) remain elusive, it has long been regarded that pathology in the CA2 hippocampal subfield is characteristic of Lewy body dementias, including dementia in PD (PDD). Early non-human primate tracer studies demonstrated connections from the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB, Ch2) to the hippocampus. However, the relationship between Lewy pathology of the CA2 subfield and cholinergic fibres has not been explored. Therefore, in this study, we investigated the burden of pathology in the CA2 subsector of PD cases with varying degrees of cognitive impairment and correlated this with the extent of septohippocampal cholinergic deficit. Hippocampal sections from 67 PD, 34 PD with mild cognitive impairment and 96 PDD cases were immunostained for tau and alpha-synuclein, and the respective pathology burden was assessed semi-quantitatively. In a subset of cases, the degree of CA2 cholinergic depletion was quantified using confocal microscopy and correlated with cholinergic neuronal loss in Ch2. We found that only cases with dementia have a significantly greater Lewy pathology, whereas cholinergic fibre depletion was evident in cases with mild cognitive impairment and this was significantly correlated with loss of cholinergic neurons in Ch2. In addition, multiple antigen immunofluorescence demonstrated colocalisation between cholinergic fibres and alpha-synuclein but not tau pathology. Such specific Lewy pathology targeting the cholinergic system within the CA2 subfield may contribute to the unique memory retrieval deficit seen in patients with Lewy body disorders, as distinct from the memory storage deficit seen in Alzheimer’s disease.

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Title: Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson’s disease with cognitive decline
Authors: Alan King Lun Liu
Tsz Wing Chau
Ernest Junwei Lim
Idil Ahmed
Raymond Chuen-Chung Chang
Michail E. Kalaitzakis
Manuel B. Graeber
Steve M. Gentleman
Ronald K. B. Pearce
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Parkinson's Disease
Pathology
Alzheimer's Disease
Alzheimer's Disease
Dementia
Dementia
Published in: Acta Neuropathologica Communications / Issue 1/2019
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-019-0717-3

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Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson’s disease with cognitive decline

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