Journal
ACTA NEUROPATHOLOGICA
Volume 128, Issue 3, Pages 411-421Publisher
SPRINGER
DOI: 10.1007/s00401-014-1302-2
Keywords
Hippocampal sclerosis; Alzheimer's disease; Neuropathology; Neurofibrillary tangles; TDP-43; GRN; TMEM106B; APOE
Categories
Funding
- Einstein Aging Study [P01 AG03949]
- Mayo ADRC Grant [P50 AG16574]
- State of Florida Alzheimer's Disease Initiative
- Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program fellowship
- Mayo Clinic ADRC Pilot grant
- Robert E Jacoby Professorship for Alzheimer's Research
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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 epsilon 4 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.
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