Brain atrophy in primary age‐related tauopathy is linked to transactive response DNA‐binding protein of 43 kDa

Abstract

Introduction: Primary age-related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent-minimal β-amyloid deposition. Transactive response DNAbinding protein of 43 kDa (TDP-43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP-43 is associated with brain atrophy in PART. Methods: We assessed the frequency of TDP-43 in PART and performed voxel-level analysis in SPM12, as well as region-of-interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP-43 and brain atrophy. Results: Of 116 PART cases, 31 (26.7%) had TDP-43. The presence of TDP-43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region-of-interest and the voxel level analyses.

Primary age-related tauopathy in a Chinese cohort

“…Expression of TDP43 was most commonly observed in the hippocampus and amygdala (Nelson et al, 2019). It was reported that PART brain atrophy was associated with TDP43 expression (Josephs et al, 2019). In the present study, expression of TDP43 was found in 67% of PART subjects, which was higher than that reported in two previous studies (Uchino et al, 2015;Elobeid et al, 2016).…”

Contribution of mixed pathology to medial temporal lobe atrophy in Alzheimer's disease

“…(2016) was used as the criteria to define positivity. Of note, TDP‐43 lesions have also been reported in individuals with PART 40,41 . In addition, it has been stated that an important portion (≈15%‐20%) of clinically diagnosed AD dementia might be attributable to LATE neuropathologic change 25 .…”

“…Another important limitation is the time between MRI and autopsy, which was on average several years, and this delay could influence the linkage between pathology observed at death and ante‐mortem imaging. However, it is important to note that this bias, with a delay of several years between the two measures, is often found in the literature linking pathology to in vivo imaging 10,40,42,43,46 . Furthermore, this time lag is more likely to influence null results than significant correlations, as in some cases pathology seen at autopsy may not have been present, or much less so, at the time of the MRI scan.…”

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

“…Similarly, the biological bases of different patterns of hemispheric lateralization in different individuals is not known. Interestingly, TDP type C has been associated with a predilection for left temporal structures in primary age-related tauopathy ( Josephs et al, 2019 ), while bilateral temporal involvement is observed in AD ( Josephs, 2014 ), thus further insights might come from a comparison of TDP type C distribution across dementias. Our novel ATL parcellation methodology shows that, irrespective of the hemisphere predominantly affected, atrophy distribution within ATLs describes a gradient whereby medial regions are more affected than lateral ones.…”