Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study

Peter Parbo; Rola Ismail; Michael Sommerauer; Morten G. Stokholm; Allan K. Hansen; Kim V. Hansen; Ali Amidi; Jeppe L. Schaldemose; Hanne Gottrup; Hans Brændgaard; Simon Fristed Eskildsen; Per Borghammer; Rainer Hinz; Joel Aanerud; David J. Brooks

doi:10.1016/j.nbd.2018.06.004

Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study

Peter Parbo^*, Rola Ismail, Michael Sommerauer, Morten G. Stokholm, Allan K. Hansen, Kim V. Hansen, Ali Amidi, Jeppe L. Schaldemose, Hanne Gottrup, Hans Brændgaard, Simon Fristed Eskildsen, Per Borghammer, Rainer Hinz, Joel Aanerud, David J. Brooks

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Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods: Six clinically probable AD and 20 MCI subjects had inflammation (¹¹C-(R)-PK11195), amyloid (¹¹C-PiB) and tau (¹⁸F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. Results: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (¹¹C-(R)-PK11195 BP_ND) and tau (¹⁸F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. Interpretation: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where ¹⁸F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Disease
Vol/bind	117
Sider (fra-til)	211-216
ISSN	0969-9961
DOI	https://doi.org/10.1016/j.nbd.2018.06.004
Status	Udgivet - sep. 2018
Udgivet eksternt	Ja

Bibliografisk note

Funding Information:
This study was financially supported by grants from the Danish Council of Independent Research [grant no. DFF-1331-00184 ], the Lundbeck Foundation [grant no. R140-2013-13245 ] and NEURODIN an AU Pilot Centre funded by the Aarhus University Research Foundation (grant no. AU-16725 ). We thank Avid Radiopharmaceuticals, Inc., for providing precursor for the 18 F-flortaucipir tracer synthesis.

Funding Information:
Dr. Brooks reports grants from Danish Council of Independent Research and the Lundbeck Foundation in support of this study and from the EU FP7 programme; lecturing fees and non-financial support from GE Healthcare and Isotopia outside the submitted work; Dr. Hinz reports grants from European Commission, during the conduct of the study; all other authors have nothing to disclose.

Publisher Copyright:
© 2018 Elsevier Inc.

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10.1016/j.nbd.2018.06.004

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Citationsformater

Parbo, P., Ismail, R., Sommerauer, M., Stokholm, M. G., Hansen, A. K., Hansen, K. V., Amidi, A., Schaldemose, J. L., Gottrup, H., Brændgaard, H., Eskildsen, S. F., Borghammer, P., Hinz, R., Aanerud, J., & Brooks, D. J. (2018). Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study. Neurobiology of Disease, 117, 211-216. https://doi.org/10.1016/j.nbd.2018.06.004

@article{32af6c6d35aa4a2c859a8d1e10c1ed97,

title = "Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study",

abstract = "Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. Results: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. Interpretation: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.",

keywords = "Alzheimer's disease, Amyloid PET, Microglial activation, Positron emission tomography, Tau PET",

author = "Peter Parbo and Rola Ismail and Michael Sommerauer and Stokholm, {Morten G.} and Hansen, {Allan K.} and Hansen, {Kim V.} and Ali Amidi and Schaldemose, {Jeppe L.} and Hanne Gottrup and Hans Br{\ae}ndgaard and Eskildsen, {Simon Fristed} and Per Borghammer and Rainer Hinz and Joel Aanerud and Brooks, {David J.}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = sep,

doi = "10.1016/j.nbd.2018.06.004",

language = "English",

volume = "117",

pages = "211--216",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press",

}

Parbo, P, Ismail, R, Sommerauer, M, Stokholm, MG, Hansen, AK, Hansen, KV, Amidi, A, Schaldemose, JL, Gottrup, H, Brændgaard, H, Eskildsen, SF, Borghammer, P, Hinz, R, Aanerud, J & Brooks, DJ 2018, 'Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study', Neurobiology of Disease, bind 117, s. 211-216. https://doi.org/10.1016/j.nbd.2018.06.004

TY - JOUR

T1 - Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study

AU - Parbo, Peter

AU - Ismail, Rola

AU - Sommerauer, Michael

AU - Stokholm, Morten G.

AU - Hansen, Allan K.

AU - Hansen, Kim V.

AU - Amidi, Ali

AU - Schaldemose, Jeppe L.

AU - Gottrup, Hanne

AU - Brændgaard, Hans

AU - Eskildsen, Simon Fristed

AU - Borghammer, Per

AU - Hinz, Rainer

AU - Aanerud, Joel

AU - Brooks, David J.

PY - 2018/9

Y1 - 2018/9

N2 - Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. Results: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. Interpretation: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.

AB - Objective: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. Results: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. Interpretation: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.

KW - Alzheimer's disease

KW - Amyloid PET

KW - Microglial activation

KW - Positron emission tomography

KW - Tau PET

U2 - 10.1016/j.nbd.2018.06.004

DO - 10.1016/j.nbd.2018.06.004

M3 - Journal article

C2 - 29902557

AN - SCOPUS:85048718443

SN - 0969-9961

VL - 117

SP - 211

EP - 216

JO - Neurobiology of Disease

JF - Neurobiology of Disease

ER -

Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study

Abstract

Bibliografisk note

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