Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study

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 (2018). Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo μPET-study. Journal of neuroinflammation, 15(1), p. 307. BioMed Central 10.1186/s12974-018-1347-6

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BACKGROUND: Causal associations between microglia activation and β-amyloid (Aβ) 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 (μPET) imaging to resolve the progression of the association between Aβ deposition and microglial responses during aging of an Aβ 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 Aβ (18F-florbetaben) and 18 kDa translocator protein (TSPO) μPET (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-Aβ). Using 3D immunohistochemistry for activated microglia (Iba-1) and histology for fibrillary Aβ (methoxy-X04), we measure microglial brain fraction relative to plaque size and the distance from plaque margins. RESULTS: Aβ-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 Aβ 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Rominger, Axel Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1742-2094

Publisher:

BioMed Central

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

01 Feb 2019 14:24

Last Modified:

01 Nov 2019 11:13

Publisher DOI:

10.1186/s12974-018-1347-6

PubMed ID:

30400912

Uncontrolled Keywords:

Aging; Alzheimer’s disease; Amyloid μPET; Microglia; Neuroinflammation; TSPO μPET

BORIS DOI:

10.7892/boris.125657

URI:

https://boris.unibe.ch/id/eprint/125657

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