Olfactory Epithelium Amyloid-β and Paired Helical Filament-tau Pathology in Alzheimer Disease

Objective: Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, alpha-synuclein, and amyloid-beta lesions occur early and severely in cerebral regions of the olfactory system, and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, and disease specificity, and the relationships of OE pathology to brain pathology have not been established. Methods: We investigated the pathological expression of amyloid-beta, PHFtau, alpha-synuclein, and TDP-43 in post-mortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. Results: Amyloid-beta was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. alpha-synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. amyloid-beta and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical A beta and PHFtau lesion ratings in the brain. Interpretation: These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-beta and PHFtau measurement in OE as a biomarker for AD. ANN NEUROL 2010;67:462-469