Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R2 relaxation rate: an ex-vivo MRI and pathology investigation

Neurobiol Aging. 2022 Sep:117:128-138. doi: 10.1016/j.neurobiolaging.2022.05.009. Epub 2022 May 28.


Limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is common in persons older than 80 years of age and is associated with cognitive decline and increased likelihood of dementia. The MRI signature of LATE-NC has not been fully determined. In this study, the association of LATE-NC with the transverse relaxation rate, R2, was investigated in a large number of community-based older adults. Cerebral hemispheres from 738 participants of the Rush Memory and Aging Project, Religious Orders Study, and Minority Aging Research Study, were imaged ex-vivo with multi-echo spin-echo MRI and underwent detailed neuropathologic examination. Voxel-wise analysis revealed a novel spatial pattern of lower R2 for higher LATE-NC stage, controlling for other neuropathologies and demographics. This pattern was consistent with the distribution of LATE-NC in gray matter, and also involved white matter providing temporo-temporal, fronto-temporal, and temporo-basal ganglia connectivity. Furthermore, analysis at different LATE-NC stages showed that R2 imaging may capture the general progression of LATE-NC, but only when TDP-43 inclusions extend beyond the amygdala.

Keywords: Ex-vivo; Limbic predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC); MRI; Pathology; R(2); Transactive response DNA binding protein of 43kDa (TDP-43).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / pathology
  • Brain / metabolism
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / etiology
  • DNA-Binding Proteins / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Nervous System Diseases* / pathology
  • TDP-43 Proteinopathies* / diagnostic imaging
  • TDP-43 Proteinopathies* / metabolism
  • White Matter* / pathology


  • DNA-Binding Proteins