Autopsied centenarian case of Alzheimer's disease combined with hippocampal sclerosis, TDP-43, and α-synuclein pathologies.

A Japanese woman showed slowly progressive memory disturbance starting at the age of 84 years, and disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, whereas the atrophy of the frontal lobe was considerably mild for her age. Behavioral and psychological symptoms of dementia were relatively inconspicuous during the disease course. Apolipoprotein E gene analysis showed ε3/ε4 heterozygosity. She died at the age of 100 years and she was clinically diagnosed as having Alzheimer's disease (AD). Autopsy revealed numerous neurofibrillary tangles, particularly in the hippocampal region, and extensively distributed senile plaques in the brain. Although the findings were compatible with the pathological criteria for AD, combined pathologies of hippocampal sclerosis, trans-activation response DNA-binding protein 43 kDa, and α-synuclein were also revealed. We believe that the clinicopathological findings of the present case are of significance for the diagnosis of elderly dementia and pathogenesis of AD.