Differential diagnosis of amnestic dementia patients based on an FDG-PET signature of autopsy-confirmed LATE-NC

Alzheimers Dement. 2023 Apr;19(4):1234-1244. doi: 10.1002/alz.12763. Epub 2022 Aug 15.

Abstract

Introduction: Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is common in advanced age and can underlie a clinical presentation mimicking Alzheimer's disease (AD). We studied whether an autopsy-derived fluorodeoxyglucose positron emission tomography (FDG-PET) signature of LATE-NC provides clinical utility for differential diagnosis of amnestic dementia patients.

Methods: Ante mortem FDG-PET patterns from autopsy-confirmed LATE-NC (N = 7) and AD (N = 23) patients were used to stratify an independent cohort of clinically diagnosed AD dementia patients (N = 242) based on individual FDG-PET profiles.

Results: Autopsy-confirmed LATE-NC and AD groups showed markedly distinct temporo-limbic and temporo-parietal FDG-PET patterns, respectively. Clinically diagnosed AD dementia patients showing a LATE-NC-like FDG-PET pattern (N = 25, 10%) were significantly older, showed less abnormal AD biomarker levels, lower APOE ε4, and higher TMEM106B risk allele load. Clinically, they exhibited a more memory-predominant profile and a generally slower disease course.

Discussion: An autopsy-derived temporo-limbic FDG-PET signature identifies older amnestic patients whose clinical, genetic, and molecular biomarker features are consistent with underlying LATE-NC.

Keywords: TDP-43; TMEM106B; amyloid; apolipoprotein E; autopsy; fluorodeoxyglucose positron emission tomography; hippocampal sclerosis; limbic age-related TDP-43 encephalopathy; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Autopsy
  • Biomarkers
  • Brain / pathology
  • Diagnosis, Differential
  • Fluorodeoxyglucose F18*
  • Humans
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Positron-Emission Tomography / methods

Substances

  • Fluorodeoxyglucose F18
  • Biomarkers
  • TMEM106B protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins