Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [C-11]ABP688 PET imaging and ex vivo immunoblotting

作者：Fang Xiaotian T; Eriksson Jonas; Antoni Gunnar; Yngve Ulrika; Cato Linda; Lannfelt Lars; Sehlin Dag; Syvanen Stina^*

来源：Neuropharmacology, 2017, 113: 293-300.

DOI：10.1016/j.neuropharm.2016.10.009

• PET
• Alzheimer's disease
• mGluR5
• [C-11] ABP688

Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (A beta) into insoluble plaques. Intermediates, A beta oligomers (A beta o), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [C-11]PIB, binds and visualizes A beta plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. A beta o alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning. In order to convey these neurotoxic effects, A beta o requires interaction with the metabotropic glutamate 5 receptor (mGluR5). The aim was to investigate in vivo mGluR5 changes in an A beta pathology model using PET. Wild type C57/BL6 (wt) and A beta PP transgenic mice (tg-ArcSwe), 4, 8, and 16 months old, were PET scanned with [C-11]ABP688, which is highly specific to mGluR5, to investigate changes in mGluR5. Mouse brains were extracted postscan and mGluR5 and A beta protofibril levels were assessed with immunoblotting and ELISA respectively. Receptor-dense brain regions (hippocampus, thalamus, and striatum) displayed higher [C-11]ABP688 concentrations corresponding to mGluR5 expression pattern. Mice had similar uptake levels of [C-11]ABP688 regardless of genotype or age. Immunoblotting revealed general decline in mGluR5 expression and elevated levels of mGluR5 in 16 months old tg-ArcSwe compared with wt mice. [C-11]ABP688 could visualize mGluR5 in the mouse brain. In conclusion, mGluR5 levels were found to decrease with age and tended to be higher in tg-ArcSwe compared with wt mice, however these changes could not be quantified with PET.

• 出版日期2017-2