Olfactory epithelium amyloid-β and paired helical filament-tau pathology in Alzheimer disease

Authors

  • Steven E. Arnold MD,

    Corresponding author
    1. Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA
    2. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
    3. Department of Neurology, University of Pennsylvania, Philadelphia, PA
    • PENN Memory Center, University of Pennsylvania, 3615 Chestnut Street, Philadelphia, PA 19104
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  • Edward B. Lee MD, PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA
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  • Paul J. Moberg PhD,

    1. Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA
    2. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
    3. Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA
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  • Lauren Stutzbach BA,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA
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  • Hala Kazi BS,

    1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
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  • Li-Ying Han MS,

    1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA
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  • Virginia M. Y. Lee PhD,

    1. Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA
    2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA
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  • John Q. Trojanowski MD, PhD

    1. Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA
    2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA
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Abstract

Objective

Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, α-synuclein, and amyloid-β 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-β, PHFtau, α-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases.

Results

Amyloid-β 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. α-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-β and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical Aβ 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-β and PHFtau measurement in OE as a biomarker for AD. ANN NEUROL 2010;67:462–469

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