Differential clinicopathologic and genetic features of late-onset amnestic dementias

Melissa E. Murray, Ashley Cannon, Neill R. Graff-Radford, Amanda M. Liesinger, Nicola J. Rutherford, Owen A. Ross, Ranjan Duara, Minerva M. Carrasquillo, Rosa Rademakers, Dennis W. Dickson

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Hippocampal sclerosis of the elderly (HpScl) and Alzheimer's disease (AD), especially the limbic-predominant subtype (LP-AD), are amnestic syndromes that can be difficult to distinguish. To complicate matters, a subset has concomitant HpScl and AD (HpScl-AD). We examined a large cohort of autopsy-confirmed cases of HpScl, HpScl-AD, LP-AD, and typical AD to identify distinct clinical, genetic, and pathologic characteristics. HpScl cases were significantly older at death and had a substantially slower rate of cognitive decline than the AD subtypes. Genetic analysis revealed that the AD groups (AD, LP-AD, and HpScl-AD) were more likely to be APOE ε4 carriers. In contrast, the HpScl groups (HpScl and HpScl-AD) were more likely to exhibit genetic variants in GRN and TMEM106B that are associated with frontotemporal lobar degeneration. The HpScl groups had a high frequency of TDP-43 pathology that was most often Type A morphology and distribution, while typical AD and LP-AD had a significantly lower frequency of TDP-43 pathology that was most often Type B. These results suggest that HpScl and AD are pathologically and genetically distinct and non-synergistic neurodegenerative processes that present with amnestic dementia. Pure HpScl and HpScl with concomitant AD occur most often in elderly individuals.

Original languageEnglish (US)
Pages (from-to)411-421
Number of pages11
JournalActa neuropathologica
Issue number3
StatePublished - Sep 2014


  • APOE
  • Alzheimer's disease
  • GRN
  • Hippocampal sclerosis
  • Neurofibrillary tangles
  • Neuropathology
  • TDP-43
  • TMEM106B

ASJC Scopus subject areas

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


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