Olfactory impairment is related to tau pathology and neuroinflammation in Alzheimer’s disease

Abstract

Background: Olfactory impairment is evident in Alzheimers disease (AD), however, its precise relationships with in vivo measures of tau pathology and neuroinflammation are not well understood. Objective: 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. Methods: 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 and fifty-three underwent 11C-PBR28 PET to measure tau pathology and neuroinflammation, respectively. Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau) and beta;-amyloid (AB42). Results: 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). Conclusions: Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. That amyloid-positivity and cognitive impairment are independently associated with odor identification suggests that low UPSIT performance may signify risk of AD pathophysiology in cognitively normal individuals and that impaired odor identification is associated with AD and non-AD-related neurodegeneration.