Alzheimer's disease neuropathologic changes in semantic dementia

Abstract

Neuropathologic change underlying primary progressive aphasia (PPA) most commonly includes one of the frontotemporal lobar degenerations, such as FTLD-tau or FTLD-ubiquitin. The next most frequent etiology of PPA is Alzheimer's disease (AD). We describe 5 subjects with clinical diagnoses of semantic dementia, who underwent longitudinal clinical evaluation and postmortem neuropathology examination of the central nervous system. This case series examines retrospectively which clinical parameters might have pointed to the neuropathological diagnosis of AD. Conclusion: family history of late onset dementia, APOEε4 status, combined features of semantic dementia and progressive non-fluent aphasia present early in illness, or generalized seizures, may indicate AD as the underlying pathology of semantic dementia.

Keywords:

• Primary progressive aphasia
• Semantic dementia
• Progressive non-fluent aphasia
• Alzheimer's disease
• Ubiquitin
• Tau

We are grateful to the patients and families who generously participated in this study, expressly to help others affected with frontotemporal dementias. We also thank Dr. Daniel Geschwind and the Genetics Core of the UCLA Alzheimer's Disease Center for APOE genotyping. This work was funded by NIA Alzheimer's Disease Research Center Grant Numbers P50 AG05142, P50 AG16570, and P30 AG08017; and Department of Health Services, Alzheimer's Research Center of California Grant No. 94–20356 (TWC, AV, CM), the University of Toronto Dean's Fund for New Faculty (#457494 TWC), and an endowment to the Sam and Ida Ross Memory Clinic (TWC), and the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine (HVV).