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

Lookup NU author(s): Dr Lauren Walker, Dr Kirsty McAleese, Professor Alan Thomas, Mary Johnson, Dr Carmen Martin-Ruiz, Dr Craig Parker, Dr Sean Colloby, Professor Johannes Attems

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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-tau), amyloid-beta protein (A beta) and alpha-synuclein (alpha-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-tau, A beta and alpha-syn. The area covered by immunopositivity was measured using image analysis. cAD cases had higher HP-tau loads than both cDLB and cPDD and the distribution of HP-tau in cAD was similar to the one observed in pure AD whilst cDLB showed comparatively less hippocampal HP-tau load. cPDD cases showed lower HP-tau and A beta loads and higher alpha-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.


Publication metadata

Author(s): Walker L, McAleese KE, Thomas AJ, Johnson M, Martin-Ruiz C, Parker C, Colloby SJ, Jellinger K, Attems J

Publication type: Article

Publication status: Published

Journal: Acta Neuropathologica

Year: 2015

Volume: 129

Issue: 5

Pages: 729-748

Print publication date: 01/05/2015

Online publication date: 11/03/2015

Acceptance date: 03/03/2015

ISSN (print): 0001-6322

ISSN (electronic): 1432-0533

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00401-015-1406-3

DOI: 10.1007/s00401-015-1406-3


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