Correlation between Olfaction and Cognition Using PET Quantification of Alzheimer’s Disease Biomarkers in Intracranial Olfactory-Related Regions of 3xTg Mice

Olfactory impairment is a preclinical symptom of Alzheimer's disease (AD); however, the mechanism of olfactory dysfunction in AD is not clear. This study aims to explore the mechanism of olfactory dysfunction in AD by analyzing the correlation between olfaction and cognition using positron emission tomography (PET) quantification of biomarkers, including amyloid β (Aβ) and abnormal tau proteins in the intracranial olfactory-related regions of AD model mice, and compares PET quantification with pathological detection to explore the reliability of the transformation of PET into clinical research. A total of 14 mice, including 3xTg mice (12 months old, <i>n</i> = 7) and wild-type (WT) mice (12 months old, <i>n</i> = 7), were enrolled in the study. Behavioral experiments (olfactory: buried food test, cognitive: Morris water maze) were performed to assess whether the mice had abnormal olfactory and cognitive functions. PET quantified Aβ and abnormal tau in olfactory-related regions. The expression and distribution of Aβ and phosphorylated tau were observed by immunofluorescence. Compared with WT mice, 3xTg mice had olfactory and cognitive impairments. Quantitative PET and immunofluorescence showed that 3xTg mice had significantly more Aβ and abnormal tau accumulation in olfactory areas than did WT mice. The deposition of Aβ and phosphorylated tau in olfactory-related regions of 3xTg mice suggests a potential link between olfactory pathology and AD progression. The elevated uptake of Aβ and tau PET in the olfactory-related regions further highlights the potential of olfactory-targeted molecular imaging as a noninvasive biomarker for AD detection.