Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

Autor: Wisse LEM; Department of Diagnostic Radiology, Lund University, Klinikgatan 13b, Lund, Sweden. lemwisse@gmail.com.; Department of Radiology, University of Pennsylvania, Philadelphia, USA. lemwisse@gmail.com., Ravikumar S; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Ittyerah R; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Lim S; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Lane J; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Bedard ML; Department of Pharmacology, University of North Carolina At Chapel Hill, Chapel Hill, USA., Xie L; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Das SR; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Schuck T; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA., Grossman M; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Lee EB; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA., Tisdall MD; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Prabhakaran K; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Detre JA; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Mizsei G; Department of Radiology, University of Pennsylvania, Philadelphia, USA., Trojanowski JQ; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA., Artacho-Pérula E; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., de Iñiguez de Onzono Martin MM; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., M Arroyo-Jiménez M; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Muñoz Lopez M; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Molina Romero FJ; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., P Marcos Rabal M; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Cebada Sánchez S; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Delgado González JC; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., de la Rosa Prieto C; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Córcoles Parada M; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Wolk DA; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Irwin DJ; Department of Neurology, University of Pennsylvania, Philadelphia, USA.; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, USA., Insausti R; Human Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla La Mancha, Albacete, Spain., Yushkevich PA; Department of Radiology, University of Pennsylvania, Philadelphia, USA.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2021 Jul 21; Vol. 9 (1), pp. 128. Date of Electronic Publication: 2021 Jul 21.
DOI: 10.1186/s40478-021-01225-3
Abstrakt: 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 3 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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