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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer's disease : a longitudinal PET study. / Ismail, Rola; Parbo, Peter; Madsen, Lasse Stensvig et al.

In: Journal of Neuroinflammation, Vol. 17, No. 1, 151, 2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{20fac6c7278c45c4b514c6663e89a3f5,
title = "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 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.",
keywords = "Alzheimer, Neuroinflammation, beta-amyloid, Tau, Microglia, PET, MCI, PK11195, PiB, Flortaucipir, POSITRON-EMISSION-TOMOGRAPHY, MILD COGNITIVE IMPAIRMENT, MICROGLIAL ACTIVATION, BRAIN, MRI, EXTRACTION, PLAQUES, TANGLES, LOAD",
author = "Rola Ismail and Peter Parbo and Madsen, {Lasse Stensvig} and Hansen, {Allan K} and Hansen, {Kim V} and Schaldemose, {Jeppe L} and Kjeldsen, {Pernille L} and Stokholm, {Morten G} and Hanne Gottrup and Eskildsen, {Simon F} and Brooks, {David J}",
year = "2020",
doi = "10.1186/s12974-020-01820-6",
language = "English",
volume = "17",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer's disease

T2 - a longitudinal PET study

AU - Ismail, Rola

AU - Parbo, Peter

AU - Madsen, Lasse Stensvig

AU - Hansen, Allan K

AU - Hansen, Kim V

AU - Schaldemose, Jeppe L

AU - Kjeldsen, Pernille L

AU - Stokholm, Morten G

AU - Gottrup, Hanne

AU - Eskildsen, Simon F

AU - Brooks, David J

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Alzheimer

KW - Neuroinflammation

KW - beta-amyloid

KW - Tau

KW - Microglia

KW - PET

KW - MCI

KW - PK11195

KW - PiB

KW - Flortaucipir

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - MILD COGNITIVE IMPAIRMENT

KW - MICROGLIAL ACTIVATION

KW - BRAIN

KW - MRI

KW - EXTRACTION

KW - PLAQUES

KW - TANGLES

KW - LOAD

U2 - 10.1186/s12974-020-01820-6

DO - 10.1186/s12974-020-01820-6

M3 - Journal article

C2 - 32375809

VL - 17

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

IS - 1

M1 - 151

ER -