Differential clinicopathologic and genetic features of late-onset amnestic dementias

Academic Article


  • 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. © 2014 Springer-Verlag.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 20442689
  • Author List

  • Murray ME; Cannon A; Graff-Radford NR; Liesinger AM; Rutherford NJ; Ross OA; Duara R; Carrasquillo MM; Rademakers R; Dickson DW
  • Start Page

  • 411
  • End Page

  • 421
  • Volume

  • 128
  • Issue

  • 3