Potential utility of salivary gland amyloid uptake as a surrogate marker for adipose tissue and amyloid-beta dynamics based on its association with BMI and cerebral amyloid burden

Recent studies have noted an unexpected inverse correlation between body mass index (BMI) and cerebral amyloid-beta (Aβ) deposition, suggesting a potential involvement of adipose tissue in AD pathology. Given the adipose-rich nature of salivary glands, we investigated whether Aβ uptake in the salivary glands is associated with the link between BMI and cerebral Aβ deposition using¹⁸F-Florbetaben PET/CT. We analyzed data from 187 participants, classified into Aβ⁻cognitively normal (Aβ⁻CN), Aβ⁺ mild cognitive impairment (Aβ⁺MCI), and Aβ⁺ AD dementia (Aβ⁺D) groups. BMI, standardized uptake value ratio of salivary glands (SUVR_SG), and brain (SUVR_B) were quantified, and their associations were examined using Pearson correlation and multiple regression analyses. Higher BMI was correlated with increased SUVR_SG (r = 0.231, p = 0.0019) and decreased SUVR_B (r = -0.247, p = 0.0009). SUVR_SG and SUVR_B were negatively correlated (r = -0.188, p = 0.0102). Multiple regression analysis identified BMI as an independent predictor of composite brain SUVR (β = -0.0168, p = 0.0046), while SUVR_SG was marginally significant (β = -0.0714, p = 0.0701). Regionally, both BMI and SUVR_SG were significantly associated with lower SUVR_B in the striatum, precuneus, and cingulate cortex. Consistent with previous studies, BMI exhibited an inverse correlation with SUVR_B. Notably, SUVR_SG was negatively associated with SUVR_B while demonstrating a positive correlation with BMI. Interpreting SUVR_SG as a fat-related marker, these findings suggest that Aβ sequestration in adipose tissue may contribute to lower cerebral Aβ accumulation. Additional research is necessary to elucidate the underlying mechanism.