Details

Autor(en) / Beteiligte

• Blume, Tanja
• Focke, Carola
• Peters, Finn
• Deussing, Maximilian
• Albert, Nathalie L
• Lindner, Simon
• Gildehaus, Franz-Josef
• von Ungern-Sternberg, Barbara
• Ozmen, Laurence
• Baumann, Karlheinz
• Bartenstein, Peter
• Rominger, Axel
• Herms, Jochen
• Brendel, Matthias

Titel

Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo [mu]PET-study

Ist Teil von

• Journal of neuroinflammation, 2018-11, Vol.15 (1)

Ort / Verlag

BioMed Central Ltd

Erscheinungsjahr

2018

Quelle

Springer Nature - Complete Springer Journals

Beschreibungen/Notizen

• Background Causal associations between microglia activation and [beta]-amyloid (A[beta]) accumulation during the progression of Alzheimer's disease (AD) remain a matter of controversy. Therefore, we used longitudinal dual tracer in vivo small animal positron emission tomography ([mu]PET) imaging to resolve the progression of the association between A[beta] deposition and microglial responses during aging of an A[beta] mouse model. Methods APP-SL70 mice (N = 17; baseline age 3.2-8.5 months) and age-matched C57Bl/6 controls (wildtype (wt)) were investigated longitudinally for 6 months using A[beta] (18F-florbetaben) and 18 kDa translocator protein (TSPO) [mu]PET (18F-GE180). Changes in cortical binding were transformed to Z-scores relative to wt mice, and microglial activation relative to amyloidosis was defined as the Z-score difference (TSPO--A[beta]). Using 3D immunohistochemistry for activated microglia (Iba-1) and histology for fibrillary A[beta] (methoxy-X04), we measure microglial brain fraction relative to plaque size and the distance from plaque margins. Results A[beta]-PET binding increased exponentially as a function of age in APP-SL70 mice, whereas TSPO binding had an inverse U-shape growth function. Longitudinal Z-score differences declined with aging, suggesting that microglial response declined relative to increasing amyloidosis in aging APP-SL70 mice. Microglial brain volume fraction was inversely related to adjacent plaque size, while the proximity to A[beta] plaques increased with age. Conclusions Microglial activity decreases relative to ongoing amyloidosis with aging in APP-SL70 mice. The plaque-associated microglial brain fraction saturated and correlated negatively with increasing plaque size with aging. Keywords: TSPO [mu]PET, Amyloid [mu]PET, Alzheimer's disease, Neuroinflammation, Microglia, Aging