Amyloid load and translocator protein 18 kDa in APPswePS1-dE9 mice: a longitudinal study

Abstract

We studied concomitantly the level of neuroinflammation and β-amyloid (Aβ) load in the APPswePS1dE9 transgenic mouse model of Alzheimer's disease using positron emission tomography. The translocator protein 18 kDa (TSPO) tracer [(18)F]DPA-714 was used to measure neuroinflammation and [(18)F]AV-45 for Aβ load in mice at 6, 9, 12, 15, and 19 months of age. At 19 months, we also analyzed the neuroinflammatory and neuroanatomic status of mice brains. The main affected brain areas were the cortex and hippocampus, with a concomitant progression of neuroinflammation with increased amyloid burden. At 19 months, no increase in TSPO binding was observed in the cerebellum; immunostaining revealed W0-2-positive plaques, indicating that the amyloid deposits seemed not stimulate inflammation. This finding was in agreement with the observed level of microglia and astrocytes staining. Our findings provide a better understanding of the relationships between neuroinflammation and plaque accumulation in the course of the disease in this mouse model. The monitoring of both processes should be of value to validate potential therapeutic approaches.

Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe×PS1Δe9 transgenic mouse model of Alzheimer's disease

“…No other difference, particularly between WT and TG, could be found in the cerebellum standard uptake value justifying the use of the cerebellum to normalize the uptake values as previously done in this type of study (Serriere et al . ; Takkinen et al . ).…”

“…Data are expressed as uptake values normalized to the cerebellum (NUV cb ) as previously used in the same mouse model (Serriere et al . ).…”

Evaluation of Small-Animal PET Outcome Measures to Detect Disease Modification Induced by BACE Inhibition in a Transgenic Mouse Model of Alzheimer Disease

“…18 F-AV45 has been implemented in animal models to monitor changes in amyloid pathology with age (30,31). It has been shown that other amyloid tracers, such as 11 C-PiB and 18 F-florbetaben, are capable of detecting a treatment effect with amyloid-modulating therapies in transgenic mouse models (18,19).…”

Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

“…In neurodegenerative diseases and models of neurodegeneration, however, the level of TSPO expression is much lower and more widespread than in focal lesions [25–27] and is thus more difficult to detect and quantify. Hence, there is a need to develop an easy-to-perform, robust preclinical model, with low levels of TSPO expression that are clinically relevant to those observed in neurodegeneration.…”