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Clinical Manifestations.

Leslie S Gaynor1, Alaina Durant1, Shubhabrata Mukherjee2

  • 1Vanderbilt University Medical Center, Nashville, TN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease (AD) uniquely impact medial temporal lobe volume and cognitive decline. Identifying LATE-NC in life is crucial for understanding its role in dementia.

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Cognitive Aging

Background:

  • Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is prevalent in dementia, often co-occurring with Alzheimer's disease (AD).
  • Lack of in-vivo biomarkers for LATE-NC hinders clinical identification.
  • This study investigates the relationship between pathologically confirmed LATE-NC, AD, medial temporal lobe (MTL) volume, and cognitive trajectories.

Purpose of the Study:

  • To evaluate the association of LATE-NC and AD neuropathology with medial temporal lobe (MTL) subregional volumes.
  • To assess the impact of LATE-NC and AD on longitudinal cognitive decline.
  • To identify clinical correlates of LATE-NC for improved in-vivo diagnosis.

Main Methods:

  • Analysis of 846 participants (age 70+) from the AD Sequencing Project Phenotype Harmonization Consortium.
  • Harmonized longitudinal cognitive domain scores (memory, executive function, language), neuropathology, and genetic data were used.
  • 3T brain MRI scans were segmented using MUSE; linear regression and mixed-effects models assessed pathology effects on MTL volume and cognitive decline.

Main Results:

  • Both AD and LATE-NC pathology were uniquely associated with specific MTL subregional volumes, with the hippocampus linked to LATE-NC but not AD.
  • Participants with LATE-NC showed a faster rate of memory decline compared to those without LATE-NC.
  • AD pathology was associated with accelerated decline in executive function and language.

Conclusions:

  • AD and LATE-NC exhibit distinct associations with MTL volume and cognitive decline patterns.
  • Understanding the clinical presentation of LATE-NC is vital for its in-life identification.
  • This research supports future studies on LATE-NC pathogenesis and clinical management.