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Acta Neuropathologica

, Volume 129, Issue 5, pp 729–748 | Cite as

Neuropathologically mixed Alzheimer’s and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes

  • Lauren Walker
  • Kirsty E. McAleese
  • Alan J. Thomas
  • Mary Johnson
  • Carmen Martin-Ruiz
  • Craig Parker
  • Sean J. Colloby
  • Kurt Jellinger
  • Johannes AttemsEmail author
Original Paper

Abstract

Multiple different pathological protein aggregates are frequently seen in human postmortem brains and hence mixed pathology is common. Mixed dementia on the other hand is less frequent and neuropathologically should only be diagnosed if criteria for more than one full blown disease are met. We quantitatively measured the amount of hyperphosphorylated microtubule associated tau (HP-τ), amyloid-β protein (Aβ) and α-synuclein (α-syn) in cases that were neuropathologically diagnosed as mixed Alzheimer’s disease (AD) and neocortical Lewy body disease (LBD) but clinically presented either as dementia due to AD or LBD, the latter including dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Our study group consisted of 28 cases (mean age, 76.11 SE: ±1.29 years; m:f, 17:11) of which 19 were neuropathologically diagnosed as mixed AD/DLB. Clinically, 8 mixed AD/DLB cases were diagnosed as AD (cAD), 8 as DLB (cDLB) and 3 as PDD (cPDD). In addition, we investigated cases that were both clinically and neuropathologically diagnosed as either AD (pure AD; n = 5) or DLB/neocortical LBD (pure DLB; n = 4). Sections from neocortical, limbic and subcortical areas were stained with antibodies against HP-τ, Aβ and α-syn. The area covered by immunopositivity was measured using image analysis. cAD cases had higher HP-τ loads than both cDLB and cPDD and the distribution of HP-τ in cAD was similar to the one observed in pure AD whilst cDLB showed comparatively less hippocampal HP-τ load. cPDD cases showed lower HP-τ and Aβ loads and higher α-syn loads. Here, we show that in neuropathologically mixed AD/DLB cases both the amount and the topographical distribution of pathological protein aggregates differed between distinct clinical phenotypes. Large-scale clinicopathological correlative studies using a quantitative methodology are warranted to further elucidate the neuropathological correlate of clinical symptoms in cases with mixed pathology.

Keywords

Alzheimer’s disease Lewy body disease Mixed dementia Quantitative neuropathology 

Notes

Acknowledgments

We are very grateful to the individuals who kindly donated their brains to the Newcastle Brain Tissue Resource. We thank Mrs Lynne Ramsay, Mrs Ros Hall and Mrs Claire Kolenda for excellent technical assistance. The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-related disease and the Biomedical Research Unit for Lewy body dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (R:CH/ML/0712), the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Lauren Walker
    • 1
  • Kirsty E. McAleese
    • 1
  • Alan J. Thomas
    • 1
  • Mary Johnson
    • 1
  • Carmen Martin-Ruiz
    • 1
  • Craig Parker
    • 1
  • Sean J. Colloby
    • 1
  • Kurt Jellinger
    • 2
  • Johannes Attems
    • 1
    Email author
  1. 1.Institute of Neuroscience and Institute for AgeingNewcastle UniversityNewcastle upon TyneUK
  2. 2.Institute of Clinical NeurobiologyViennaAustria

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