Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem M...

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Published in:	Acta neuropathologica communications Vol. 9; no. 1; p. 128
Main Authors:	Wisse, L E M, Ravikumar, S, Ittyerah, R, Lim, S, Lane, J, Bedard, M L, Xie, L, Das, S R, Schuck, T, Grossman, M, Lee, E B, Tisdall, M D, Prabhakaran, K, Detre, J A, Mizsei, G, Trojanowski, J Q, Artacho-Pérula, E, de Iñiguez de Onzono Martin, M M, M Arroyo-Jiménez, M, Muñoz Lopez, M, Molina Romero, F J, P Marcos Rabal, M, Cebada Sánchez, S, Delgado González, J C, de la Rosa Prieto, C, Córcoles Parada, M, Wolk, D A, Irwin, D J, Insausti, R, Yushkevich, P A
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 21-07-2021 BioMed Central BMC
Subjects:	Adult Aged Aged, 80 and over alpha-Synuclein - metabolism Alzheimer Disease - diagnostic imaging Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Atrophy Basic Medicine Biomarkers Brain Brain Cortical Thickness Brain research CA1 Region, Hippocampal - diagnostic imaging CA1 Region, Hippocampal - metabolism CA1 Region, Hippocampal - pathology Case-Control Studies DNA-Binding Proteins - metabolism Entorhinal Cortex - diagnostic imaging Entorhinal Cortex - metabolism Entorhinal Cortex - pathology Female Frontotemporal Lobar Degeneration - diagnostic imaging Frontotemporal Lobar Degeneration - metabolism Frontotemporal Lobar Degeneration - pathology Hippocampus - diagnostic imaging Hippocampus - metabolism Hippocampus - pathology Humans Laboratories Lewy Body Disease - diagnostic imaging Lewy Body Disease - metabolism Lewy Body Disease - pathology Magnetic Resonance Imaging Male Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicine, Experimental Medicinska och farmaceutiska grundvetenskaper Middle Aged Neurodegeneration Neurodegenerative Diseases - diagnostic imaging Neurodegenerative Diseases - metabolism Neurodegenerative Diseases - pathology Neurofibrillary Tangles - pathology Neuropathology Neurosciences Neurovetenskaper Parahippocampal Gyrus - diagnostic imaging Parahippocampal Gyrus - metabolism Parahippocampal Gyrus - pathology Pathology Pick Disease of the Brain - diagnostic imaging Pick Disease of the Brain - metabolism Pick Disease of the Brain - pathology Plaque, Amyloid - pathology Protein binding Supranuclear Palsy, Progressive - diagnostic imaging Supranuclear Palsy, Progressive - metabolism Supranuclear Palsy, Progressive - pathology tau Proteins - metabolism Temporal Lobe - diagnostic imaging Temporal Lobe - metabolism Temporal Lobe - pathology
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Summary:	The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2051-5960 2051-5960
DOI:	10.1186/s40478-021-01225-3