Olfactory Impairment Is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease.

Abstract

Olfactory impairment is evident in Alzheimer's disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ42). Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01). Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.NCT Registration Numbers: NCT03373604; NCT02831283.