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Journal of Neural Transmission

, Volume 124, Issue 6, pp 671–683

First Online: 06 March 2017Received: 18 January 2017Accepted: 24 February 2017DOI: 10.1007-s00702-017-1702-2

Cite this article as: Walker, L., McAleese, K.E., Johnson, M. et al. J Neural Transm 2017 124: 671. doi:10.1007-s00702-017-1702-2

Abstract

A tissue microarray TMA has previously been developed for use in assessment of neurodegenerative diseases. We investigated the variation of pathology loads in semi-quantitative score categories and how pathology load related to disease progression. Post-mortem tissue from 146 cases were used; Alzheimer’s disease AD n = 36, Lewy body disease LBD n = 56, mixed AD-dementia with Lewy bodies n = 14 and controls n = 40. TMA blocks one per case were constructed using tissue cores from 15 brain regions including cortical and subcortical regions. TMA tissue sections were stained for hyperphosphorylated tau HP-T, β amyloid and α-synuclein αsyn, and quantified using an automated image analysis system. Cases classified as Braak stage VI displayed a wide variation in HP-T pathology in the entorhinal cortex interquartile range 4.13–44.03%. The interquartile range for β amyloid in frontal cortex in cases classified as Thal phase 5 was 6.75–17.03% and for αsyn in the cingulate in cases classified as McKeith neocortical LBD was 0.04–0.58%. In AD and control cases, HP-T load predicted the Braak stage p < 0.001, β amyloid load predicted Thal phase p < 0.001 and αsyn load in LBD cases predicted McKeith type of LBD p < 0.001. Quantitative data from TMA assessment highlight the range in pathological load across cases classified with ‘severe’ pathology and is beneficial to further elucidate the heterogeneity of neurodegenerative diseases. Quantifying pathology in multiple brain regions may allow identification of novel clinico-pathological phenotypes for the improvement of intra vitam stratification of clinical cohorts according to underlying pathologies.

KeywordsTissue microarray Quantification Alzheimer’s disease Lewy body disease On the occasion of Professor Kurt Jellinger’s 85th birthday for his continuous support, inspiration and friendship!





Author: Lauren Walker - Kirsty E. McAleese - Mary Johnson - Ahmad A. Khundakar - Daniel Erskine - Alan J. Thomas - Ian G. McKei

Source: https://link.springer.com/







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