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 mm3 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.

中文翻译：

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多病理学对内侧颞叶亚区域神经变性的下游影响

内侧颞叶（MTL）是神经退行性病变的病灶，因此是研究多病理学的重要区域。我们研究了神经退行性病理学与使用高分辨率死后 MRI 测量的不同 MTL 亚区域厚度之间的关联。对 58 名患有此病的个体的海马和内嗅皮层 (ERC) 中的 Tau、TAR DNA 结合蛋白 43 (TDP-43)、淀粉样蛋白-β 和 α-突触核蛋白病理学进行了 0（缺失）—3（严重）评分。无神经退行性疾病（中位年龄 75.0 岁，60.3% 为男性）。ERC、布罗德曼区 (BA) 35 和 36、海马旁皮层、下托、阿蒙角 (CA)1 和放射层腔隙分子层 (SRLM) 的厚度测量源自 0.2 × 0.2 × 0。使用半自动方法对从对侧半球切除的 MTL 标本进行 2 mm3 尸检 MRI 扫描。在神经退行性病理学和厚度之间进行斯皮尔曼等级相关，校正年龄、性别和半球，包括模型中的所有四种蛋白质病。我们发现 (1) TDP-43 与所有分区的厚度 (r = − 0.27 至 r = − 0.46) 以及 (2) tau 与 BA35 (r = − 0.31) 和 SRLM 厚度 (r = − 0.33) 显着相关。在淀粉样蛋白-β 和 TDP-43 阴性病例中，我们发现 tau 蛋白与 ERC (r = − 0.40)、BA35 (r = − 0.55)、下托 (r = − 0.42) 和 CA1 厚度 (r = − 0.47) 存在显着相关性）。这个独特的数据集显示了与 TDP-43 病理学相关的广泛 MTL 萎缩，以及 Braak 分期和 tau 病理学早期受影响区域的萎缩。而且，