Olfactory epithelium amyloid-beta 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 postmortem 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 Abeta and PHFtau lesion ratings in the brain.


CONCLUSIONS
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.
Arnold
Steven E
SE
Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA 19104, USA. steven.arnold@uphs.upenn.edu
Lee
Edward B
EB
Moberg
Paul J
PJ
Stutzbach
Lauren
L
Kazi
Hala
H
Han
Li-Ying
LY
Lee
Virginia M Y
VM
Trojanowski
John Q
JQ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D009831:Olfactory Mucosa / Q000378:metabolism* / Q000473:pathology*; D013223:Statistics as Topic; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; D051844:alpha-Synuclein; D016875:tau Proteins