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Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes.
Acta Neuropathol. 2015 May; 129(5):729-48.AN

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.

Authors+Show Affiliations

Institute of Neuroscience and Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, NE4 5PL, Newcastle upon Tyne, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25758940

Citation

Walker, Lauren, et al. "Neuropathologically Mixed Alzheimer's and Lewy Body Disease: Burden of Pathological Protein Aggregates Differs Between Clinical Phenotypes." Acta Neuropathologica, vol. 129, no. 5, 2015, pp. 729-48.
Walker L, McAleese KE, Thomas AJ, et al. Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathol. 2015;129(5):729-48.
Walker, L., McAleese, K. E., Thomas, A. J., Johnson, M., Martin-Ruiz, C., Parker, C., Colloby, S. J., Jellinger, K., & Attems, J. (2015). Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathologica, 129(5), 729-48. https://doi.org/10.1007/s00401-015-1406-3
Walker L, et al. Neuropathologically Mixed Alzheimer's and Lewy Body Disease: Burden of Pathological Protein Aggregates Differs Between Clinical Phenotypes. Acta Neuropathol. 2015;129(5):729-48. PubMed PMID: 25758940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes. AU - Walker,Lauren, AU - McAleese,Kirsty E, AU - Thomas,Alan J, AU - Johnson,Mary, AU - Martin-Ruiz,Carmen, AU - Parker,Craig, AU - Colloby,Sean J, AU - Jellinger,Kurt, AU - Attems,Johannes, Y1 - 2015/03/11/ PY - 2015/01/21/received PY - 2015/03/03/accepted PY - 2015/03/03/revised PY - 2015/3/12/entrez PY - 2015/3/12/pubmed PY - 2016/1/12/medline SP - 729 EP - 48 JF - Acta neuropathologica JO - Acta Neuropathol VL - 129 IS - 5 N2 - 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. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/25758940/Neuropathologically_mixed_Alzheimer's_and_Lewy_body_disease:_burden_of_pathological_protein_aggregates_differs_between_clinical_phenotypes_ DB - PRIME DP - Unbound Medicine ER -