Olfactory bulb Amyloid-beta correlates with brain Thal amyloid phase and severity of cognitive impairment

The Alzheimer disease (AD) neuropathological hallmarks amyloid beta (A beta) and tau neurofibrillary (NF) pathology have been reported in the olfactory bulb (OB) in aging and in different neurodegenerative diseases, which coincides with frequently reported olfactory dysfunction in these conditions. To better understand when the OB is affected in relation to the hierarchical progression of A beta throughout the brain and whether OB pathology might be an indicator of AD severity, we assessed the presence of OB A beta and tau NF pathology in an autopsy cohort of 158 non demented control and 173 AD dementia cases. OB A beta was found in less than 5% of cases in lower Thal phases 0 and 1, in 20% of cases in phase 2, in 60% of cases in phase 3 and in more than 80% of cases in higher Thal phases 4 and 5. OB A beta and tau pathology significantly predicted a Thal phase greater than 3, a Braak NF stage greater than 4, and an MMSE score lower than 24. While OB tau pathology is almost universal in the elderly and therefore is not a good predictor of AD severity, OB A beta pathology coincides with clinically-manifest AD and might prove to be a useful biomarker of the extent of brain spread of both amyloid and tau pathology.