In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
Abstract:
The medial temporal lobe (MTL) is a hotspot of different neurodegenerative pathologies, and recent studies have shown associations of severity of pathology with atrophy measured on antemortem MRI. However, these studies are limited by the interval between time of scan and death and the relatively low resolution of the commonly acquired in vivo MRI scans, limiting the granularity of the regions being measured. We investigate the association of different neurodegenerative pathologies, particularly TDP‐43, and the thickness of different MTL subregions measured on high‐resolution postmortem MRI. As prior work suggests an anterior‐to‐posterior gradient of atrophy for TDP‐43 in frontotemporal dementia spectrum disorders and Limbic‐predominant Age‐related TDP‐43 Encephalopathy (LATE), we also examined differences along the long axis of the MTL. Method Tau, TDP‐43, β‐amyloid and α‐synuclein pathology were rated (0‐absent – 3‐frequent) in the hippocampus and entorhinal cortex (ERC) of 35 individuals with and without neurodegenerative diseases (Table 1). Thickness measurements were obtained from 0.2x0.2x0.2 mm 3 post‐mortem MRI scans of excised MTL specimens from the contralateral hemisphere (Figure 1) in the ERC, Brodmann Area 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare. For each region, thickness was measured at an anterior and posterior location using a semi‐automated approach (Figure 2). Spearman’s rank correlations were performed, correcting for age, sex and hemisphere, including all four proteinopathies in the model. Result We find strong negative associations of TDP‐43 with thickness in all cortical MTL regions (Table 2, Figure 3) and with CA1, averaged over the two locations. We repeated the analyses for the thickness measurements separately in the anterior and posterior locations, but did not find a clear difference along the longitudinal axis. This is potentially due to the severity of the TDP‐43 pathology. Conclusion In this unique dataset with neurodegenerative pathologies and high‐resolution scans of the MTL, preliminary results show strong associations between TDP‐43 pathology and atrophy in several MTL subregions. As this dataset continues to grow, we will be able to tease apart the effects of multiple MTL pathologies at a subregional level.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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