[18F]flutemetamol uptake in the colon of a memory clinic population and its association with brain amyloidosis and the gut microbiota profile: an exploratory study.

Purpose: Some Alzheimer's disease (AD) patients report gastro-intestinal symptoms and present alterations in the gut microbiota (GM) composition. Elevated colonic amyloid immunoreactivity has been shown in patients and animal models. We evaluated the colonic uptake of the amyloid positron emission tomography (PET) imaging agent [18F]flutemetamol (FMM) in a memory clinic population and investigated its association with brain amyloidosis and GM composition.

Methods: Forty-five participants underwent (i) abdominal and cerebral FMM PET, acquired at 40 (early phase) and 120 min (late phase) after tracer injection, (ii) abdominal computed tomography, and (iii) cerebral T1-weighted MRI. Colonic standardized uptake value ratio (SUVr) was determined through manual tracing and automatic segmentation (TotalSegmentator), using the aortic blood signal as a reference region. Fecal GM composition was assessed using 16 S rRNA sequencing. Amyloid positive (A+) and negative (A-) participants, based on cortical FMM quantification (PetSurfer), were compared in terms of SUVr and GM features.

Results: Increased colonic early SUVr was reported in A+ than A- (manual, p =.008; automated, p =.035). Altered GM composition was found in A + as shown by lower Pielou's evenness (p =.023), lower abundance of Eubacterium hallii group, and higher abundance of several genera. High UC5-1-2E3 abundance positively correlated with high colonic early SUVr (whole group: manual, p =.012, automated, p =.082; A+: manual, p =.074; automated, p =.016).

Conclusion: This exploratory study showed that subjects with cerebral amyloidosis have greater colonic FMM uptake than subjects with normal cerebral amyloid load, correlating with altered GM composition. Further analysis is needed to determine if these changes denote amyloid-related changes or other phenomena.