MicroPET Imaging Assessment of Brain Tau and Amyloid Deposition in 6 x Tg Alzheimer's Disease Model Mice

Abstract

Alzheimer's disease (AD) is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFT). Amyloid beta (A beta) and tau imaging are widely used for diagnosing and monitoring AD in clinical settings. We evaluated the pathology of a recently developed 6 x Tg - AD (6 x Tg) mouse model by crossbreeding 5 x FAD mice with mice expressing mutant (P301L) tau protein using micro-positron emission tomography (PET) image analysis. PET studies were performed in these 6 x Tg mice using [F-18]Flutemetamol, which is an amyloid PET radiotracer; [F-18]THK5351 and [F-18]MK6240, which are tau PET radiotracers; moreover, [F-18]DPA714, which is a translocator protein (TSPO) radiotracer, and comparisons were made with age-matched mice of their respective parental strains. We compared group differences in standardized uptake value ratio (SUVR), kinetic parameters, biodistribution, and histopathology. [F-18]Flutemetamol images showed prominent cortical uptake and matched well with 6E10 staining images from 2-month-old 6 x Tg mice. [F-18]Flutemetamol images showed a significant correlation with [F-18]DPA714 in the cortex and hippocampus. [F-18]THK5351 images revealed prominent hippocampal uptake and matched well with AT8 immunostaining images in 4-month-old 6 x Tg mice. Moreover, [F-18]THK5351 images were confirmed using [F-18]MK6240, which revealed significant correlations in the cortex and hippocampus. Uptake of [F-18]THK5351 or [F-18]MK6240 was highly correlated with [F-18]Flutemetamol in 4-month-old 6 x Tg mice. In conclusion, PET imaging revealed significant age-related uptake of A beta, tau, and TSPO in 6 x Tg mice, which was highly correlated with age-dependent pathology.