Acta Neuropathologica

, Volume 128, Issue 3, pp 411–421 | Cite as

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. DicksonEmail author
Original Paper


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.


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



We thank the patients and their families who donated brains to help further our knowledge in neurodegeneration. The authors would like to acknowledge Linda G. Rousseau, Virginia R. Phillips, and Monica Castanedes-Casey for tissue processing and staining. The project was supported by the Einstein Aging Study (P01 AG03949), Mayo ADRC Grant (P50 AG16574), and the State of Florida Alzheimer’s Disease Initiative. MEM and this project were supported by the Robert and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program fellowship and the Mayo Clinic ADRC Pilot grant. DWD was supported by the Robert E Jacoby Professorship for Alzheimer’s Research.

Supplementary material

401_2014_1302_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 29 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Melissa E. Murray
    • 1
  • Ashley Cannon
    • 1
  • Neill R. Graff-Radford
    • 2
  • Amanda M. Liesinger
    • 1
  • Nicola J. Rutherford
    • 1
  • Owen A. Ross
    • 1
  • Ranjan Duara
    • 3
  • Minerva M. Carrasquillo
    • 1
  • Rosa Rademakers
    • 1
  • Dennis W. Dickson
    • 1
    Email author
  1. 1.Department of NeuroscienceMayo ClinicJacksonvilleUSA
  2. 2.Department of NeurologyMayo ClinicJacksonvilleUSA
  3. 3.Department of NeurologyMount Sinai Medical CenterFloridaUSA

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