Olfactory involvement in aging and Alzheimer's disease: an autopsy study.

Olfactory dysfunction and tau pathology in the olfactory bulb increase with the severity of Alzheimer's disease. We report data of a postmortem study in the aged. 130 autopsy cases (81 female, 49 male, aged 61-102, mean 82.48 +/- 4.35 SD) years, underwent a standardized neuropathological assessment with immunohistochemical study of tau pathology in the olfactory bulb and nerve and of Alzheimer's disease using established criteria including Braak staging. All cases of definite Alzheimer's disease (Braak stages 5 and 6) (n = 40) showed large numbers of neuropil threads and neurofibrillary tangles, with amyloid deposits in 32.5% and neuritic plaques in one single case in the olfactory system. Braak stage 4 (n = 27) was associated with mild to moderate tau pathology in 85.2%, and amyloid plaques in 1.1%, Braak stage 3 (n = 28) with olfactory tau lesions in 37.0% and amyloid deposits in one single case, Braak stages 3 and 4 with olfactory tau lesions in 61.1%. Braak stage 2 (n = 15) showed olfactory tau pathology in 31.2%, whereas Braak stages 0 and 1 (n = 15) were all negative. The olfactory system tau score showed highly significant correlations with neuritic Braak stages in the brain, while both scores showed significant but low correlations with age. These data confirm previous studies demonstrating abundant tau pathology in the olfactory system in all definite Alzheimer's disease cases, in two-thirds of limbic Alzheimer's disease, and in almost one-third of non-demented elderly persons with Braak stage 2. There are strong correlations between tau pathology in the olfactory and limbic systems, both with similar increase in severity. Clinical dementia correlated with both Braak and olfactory system tau scores. Since the involvement of both systems is associated with a high risk of cognitive decline, future studies should validate the sensitivity of olfactory mucosa biopsies in the diagnosis of Alzheimer's disease.