Hippocampal sclerosis but not normal aging or Alzheimer disease is associated with TDP-43 pathology in the basal forebrain of aged persons

Matthew D. Cykowski, Hidehiro Takei, Linda J. Van Eldik, Frederick A. Schmitt, Gregory A. Jicha, Suzanne Z. Powell, Peter T. Nelson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Transactivating responsive sequence (TAR) DNA-binding protein 43-kDa (TDP-43) pathology has been described in various brain diseases, but the full anatomical distribution and clinical and biological implications of that pathology are incompletely characterized. Here, we describe TDP-43 neuropathology in the basal forebrain, hypothalamus, and adjacent nuclei in 98 individuals (mean age, 86 years; median final mini-mental state examination score, 27). On examination blinded to clinical and pathologic diagnoses, we identified TDP-43 pathology that most frequently involved the ventromedial basal forebrain in 19 individuals (19.4%). As expected, many of these brains had comorbid pathologies including those of Alzheimer disease (AD), Lewy body disease (LBD), and/or hippocampal sclerosis of aging (HS-Aging). The basal forebrain TDP-43 pathology was strongly associated with comorbid HS-Aging (odds ratio = 6.8, p = 0.001), whereas there was no significant association between basal forebrain TDP-43 pathology and either AD or LBD neuropathology. In this sample, there were some cases with apparent preclinical TDP-43 pathology in the basal forebrain that may indicate that this is an early affected area in HS-Aging. We conclude that TDP-43 pathology in the basal forebrain is strongly associated with HS-Aging. These results raise questions about a specific pathogenetic relationship between basal forebrain TDP-43 and non-HSAging comorbid diseases (AD and LBD).

Original languageEnglish (US)
Pages (from-to)397-407
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number5
DOIs
StatePublished - May 1 2016

Keywords

  • Aging
  • Alzheimer disease
  • Basal forebrain
  • Frontotemporal lobar degeneration
  • Hippocampal sclerosis
  • TDP-43

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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