The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study
Abstract 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 β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. Methods Forty-three su...
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doaj-d6cbb349346a47e69fbe4d108ae945512020-11-25T02:58:54ZengBMCJournal of Neuroinflammation1742-20942020-05-0117111110.1186/s12974-020-01820-6The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET studyRola Ismail0Peter Parbo1Lasse Stensvig Madsen2Allan K. Hansen3Kim V. Hansen4Jeppe L. Schaldemose5Pernille L. Kjeldsen6Morten G. Stokholm7Hanne Gottrup8Simon F. Eskildsen9David J. Brooks10Department of Clinical Medicine, PET-Centre, Aarhus UniversityDepartment of Nuclear Medicine and PET Centre, Aarhus University HospitalDepartment of Clinical Medicine, PET-Centre, Aarhus UniversityDepartment of Nuclear Medicine and PET Centre, Aarhus University HospitalDepartment of Nuclear Medicine and PET Centre, Aarhus University HospitalDepartment of Clinical Medicine, PET-Centre, Aarhus UniversityDepartment of Clinical Medicine, PET-Centre, Aarhus UniversityDepartment of Nuclear Medicine and PET Centre, Aarhus University HospitalDept. of Neurology, Aarhus University HospitalCentre of Functionally Integrative Neuroscience (CFIN), Aarhus UniversityDepartment of Clinical Medicine, PET-Centre, Aarhus UniversityAbstract 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 β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. Methods Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-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 significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. 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 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 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 β-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 which 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 2 years with a correlated rise in levels of inflammation. Conclusions Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer’s disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.http://link.springer.com/article/10.1186/s12974-020-01820-6AlzheimerNeuroinflammationβ-amyloidTauMicrogliaPET |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rola Ismail Peter Parbo Lasse Stensvig Madsen Allan K. Hansen Kim V. Hansen Jeppe L. Schaldemose Pernille L. Kjeldsen Morten G. Stokholm Hanne Gottrup Simon F. Eskildsen David J. Brooks |
spellingShingle |
Rola Ismail Peter Parbo Lasse Stensvig Madsen Allan K. Hansen Kim V. Hansen Jeppe L. Schaldemose Pernille L. Kjeldsen Morten G. Stokholm Hanne Gottrup Simon F. Eskildsen David J. Brooks The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study Journal of Neuroinflammation Alzheimer Neuroinflammation β-amyloid Tau Microglia PET |
author_facet |
Rola Ismail Peter Parbo Lasse Stensvig Madsen Allan K. Hansen Kim V. Hansen Jeppe L. Schaldemose Pernille L. Kjeldsen Morten G. Stokholm Hanne Gottrup Simon F. Eskildsen David J. Brooks |
author_sort |
Rola Ismail |
title |
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study |
title_short |
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study |
title_full |
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study |
title_fullStr |
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study |
title_full_unstemmed |
The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study |
title_sort |
relationships between neuroinflammation, beta-amyloid and tau deposition in alzheimer’s disease: a longitudinal pet study |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2020-05-01 |
description |
Abstract 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 β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. Methods Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-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 significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. 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 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 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 β-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 which 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 2 years with a correlated rise in levels of inflammation. Conclusions Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer’s disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation. |
topic |
Alzheimer Neuroinflammation β-amyloid Tau Microglia PET |
url |
http://link.springer.com/article/10.1186/s12974-020-01820-6 |
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