TDP-43 and Alzheimer's Disease Pathologic Subtype in Non-Amnestic Alzheimer's Disease Dementia

Aradhana Sahoo, Alexandre Bejanin, Melissa E. Murray, Nirubol Tosakulwong, Stephen D. Weigand, Amanda M. Serie, Matthew L. Senjem, Mary M. MacHulda, Joseph E. Parisi, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, Jennifer L. Whitwell, Keith A. Josephs

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: TDP-43 has been shown to be strongly associated with memory loss, smaller hippocampal volumes, and faster rates of hippocampal atrophy in Alzheimer's disease (AD) patients with an amnestic presentation. Whether TDP-43 has any clinical or anatomical associations in AD patients with non-amnestic phenotype is unknown. Objective: To determine whether TDP-43 plays a significant role in the clinic-anatomic features of non-amnestic AD. Methods: All cases with pathologically confirmed intermediate-high probability AD from 1996-2012 were identified and retrospectively sub-classified into amnestic versus non-amnestic dementia at the time of presentation. Neurofibrillary tangle counts were performed in those with a non-amnestic presentation using thioflavin-S microscopy in the hippocampus and three neocortical regions, and all cases were subtyped into hippocampal-sparing, limbic-predominant, and typical AD pathology. TDP-43 immunoreactivity was used to assess for the presence of TDP-43. Statistical analyses helped determine whether pathologic subtype or TDP-43 was more strongly associated with clinico-imaging features. Results: Out of 172 pathologically confirmed AD cases, 36 (19%) were classified as non-amnestic. Twenty-five of these 36 (69%) had typical pathology, 0 limbic-predominant pathology, and 11 (31%) hippocampal-sparing pathology. Eleven (44%) of the 25 cases with typical pathology were TDP-43+. Of the 11 cases with hippocampal-sparing pathology, 4 (36%) were TDP-43+. There were no differences in demographic, clinical, or neuroimaging features in those with TDP-43 versus those without except for older age at onset (p = 0.02) and age at death (p = 0.02) in those with TDP-43. AD pathological subtype accounted for slightly more of the variances in the neocortex than TDP-43. Conclusion: In non-amnestic AD, we find little evidence that clinical or anatomical features of the disease are related to TDP-43.

Original languageEnglish (US)
Pages (from-to)1227-1233
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2018


  • Alzheimer's disease
  • TDP-43
  • atypical AD
  • non-amnestic

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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