Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature

Eseosa T. Ighodaro, Gregory A. Jicha, Frederick A. Schmitt, Janna H. Neltner, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Taylor Duplessis, Sonya Anderson, Ela Patel, Adam Bachstetter, Linda J. Van Eldik, Peter T. Nelson

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations


Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with "hippocampal sclerosis" pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of "segmental" HS-Aging in which "sclerosis" in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of "hippocampal sclerosis" and TDP-43 pathologies in aged subjects.

Original languageEnglish
Pages (from-to)642-652
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Issue number7
StatePublished - Jul 29 2015

Bibliographical note

Publisher Copyright:
Copyright © 2015 by the American Association of Neuropathologists, Inc.


  • Biomarkers
  • Case study
  • Dementia
  • Frontotemporal lobar degeneration (FTLD)
  • Hippocampal sclerosis
  • Neuropathology
  • Oldest-old

ASJC Scopus subject areas

  • Medicine (all)


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