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 Margaret Machulda, Joseph E Parisi, Bradley F Boeve, David S Knopman, Ronald Carl Petersen, Dennis W Dickson, Jennifer Lynn Whitwell, Keith Anthony Josephs

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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
Volume64
Issue number4
DOIs
StatePublished - Jan 1 2018

Fingerprint

Alzheimer Disease
Pathology
Neurofibrillary Tangles
Neocortex
Memory Disorders
Age of Onset
Neuroimaging
Atrophy
Dementia
Microscopy
Hippocampus
Demography
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

TDP-43 and Alzheimer's Disease Pathologic Subtype in Non-Amnestic Alzheimer's Disease Dementia. / Sahoo, Aradhana; Bejanin, Alexandre; Murray, Melissa E; Tosakulwong, Nirubol; Weigand, Stephen D.; Serie, Amanda M.; Senjem, Matthew L.; Machulda, Mary Margaret; Parisi, Joseph E; Boeve, Bradley F; Knopman, David S; Petersen, Ronald Carl; Dickson, Dennis W; Whitwell, Jennifer Lynn; Josephs, Keith Anthony.

In: Journal of Alzheimer's Disease, Vol. 64, No. 4, 01.01.2018, p. 1227-1233.

Research output: Contribution to journalArticle

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T1 - TDP-43 and Alzheimer's Disease Pathologic Subtype in Non-Amnestic Alzheimer's Disease Dementia

AU - Sahoo, Aradhana

AU - Bejanin, Alexandre

AU - Murray, Melissa E

AU - Tosakulwong, Nirubol

AU - Weigand, Stephen D.

AU - Serie, Amanda M.

AU - Senjem, Matthew L.

AU - Machulda, Mary Margaret

AU - Parisi, Joseph E

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Whitwell, Jennifer Lynn

AU - Josephs, Keith Anthony

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N2 - 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.

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KW - Alzheimer's disease

KW - atypical AD

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