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The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study

Lookup NU author(s): Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated b-amyloid and tau at baseline and again after two years in prodromal Alzheimer’s disease. Methods: Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over two years to measure inflammation changes and 11C-PiB PET to determine b-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significantly altered tracer binding compated to healrthy controls at baseline and after two years and to interrogate correlations between binding of the tracers at these two time points. Results: Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer’s disease) had raised inflammation levels which significantly declined across cortical regions over two years although their b-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over two years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising b-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD and they showed no correlated inflammation levels. Finally, MCI cases who showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over two years with a correlated rise in levels of inflammation. Conclusions: Our baseline and two year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer’s disease: MCI cases with low baseline but subsequently rising b-amyloid load show correlated levels of microglial activation which then later decline when the b-amyloid load approaches AD levels. Later, as tau tangles form in b-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

Publication metadata

Author(s): Ismail R, Parbo P, Madsen LS, Hansen AK, Hansen KV, Schaldemose JL, Kjeldsen PL, Stokholm MG, Gottrup H, Eskildsen SF, Brooks DJ

Publication type: Article

Publication status: Published

Journal: Journal of Neuroinflammation

Year: 2020

Volume: 17

Acceptance date: 15/04/2020

Date deposited: 16/04/2020

ISSN (electronic): 1742-2094

Publisher: BMC


DOI: 10.1186/s12974-020-01820-6


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