Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically.

BACKGROUND

Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration.

METHODS

We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE).

RESULTS

Of the 205 dementia patients, 28 had HpScl (14%). TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%). GRN rs5848 T-allele but not APOE ε4 was associated with HpScl. In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl."

CONCLUSIONS

HpScl is common in an elderly cohort with dementia, occurring in 14% of the cases in this series, and 89% have TDP-43 pathology, often associated with a risk variant in GRN. Patients with HpScl who present after the age of 75 years often have presentations consistent with AD, but at autopsy have non-Alzheimer pathologies. Elderly patients with HpScl may be mistaken for AD.