Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

Rik Ossenkoppele, Chul Hyoung Lyoo, Carole H. Sudre, Danielle van Westen, Hanna Cho, Young Hoon Ryu, Jae Yong Choi, Ruben Smith, Olof Strandberg, Sebastian Palmqvist, Eric Westman, Richard Tsai, Joel Kramer, Adam L. Boxer, Maria L. Gorno-Tempini, Renaud La Joie, Bruce L. Miller, Gil D. Rabinovici, Oskar Hansson

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalAlzheimer's and Dementia
Volume16
Issue number2
DOIs
Publication statusPublished - 2020 Feb 1

Bibliographical note

Funding Information:
Work at Lund University was supported by the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg foundation, the Knut and Alice Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skfine University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of 18F-flutemetamol injection were sponsored by GE Healthcare. Work at UCSF was supported by National Institute on Aging grants (R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, and U54-NS092089), the Alzheimer's Association (AARF-16-443577), Tau Consortium, and the Michael J Fox foundation. Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP, 2015R1C1A2A01054507) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2017R1A2B2006694). C.H.S. is funded by the Alzheimer's Society (AS-JF-17-011). For UCSF and the BioFINDER study, the precursor of [18F]flortaucipir was provided by AVID radiopharmaceuticals. Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983, the Tau Research Consortium, the Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, and the Alzheimer's Association. He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceu- ticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest.

Funding Information:
Work at Lund University was supported by the European Research Council , the Swedish Research Council , the Marianne and Marcus Wallenberg foundation , the Knut and Alice Wallenberg foundation , the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University , the Swedish Brain Foundation , the Swedish Alzheimer Foundation , The Parkinson Foundation of Sweden, The Parkinson Research Foundation , the Skåne University Hospital Foundation , and the Swedish federal government under the ALF agreement. Doses of 18 F-flutemetamol injection were sponsored by GE Healthcare . Work at UCSF was supported by National Institute on Aging grants ( R01-AG045611 , P50-AG023501 , P01-AG19724 , R01-AG038791 , and U54-NS092089 ), the Alzheimer's Association ( AARF-16-443577 ), Tau Consortium, and the Michael J Fox foundation . Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MSIP , 2015R1C1A2A01054507 ) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning ( 2017R1A2B2006694 ). C.H.S. is funded by the Alzheimer's Society ( AS-JF-17-011 ). For UCSF and the BioFINDER study, the precursor of [ 18 F]flortaucipir was provided by AVID radiopharmaceuticals.

Funding Information:
Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare , Biogen , AVID Radiopharmaceuticals , Fujirebio , and Euroimmun . In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089 , R01AG031278 , R01AG038791 , R01AG032306 , R01AG022983 , the Tau Research Consortium , the Bluefield Project to Cure Frontotemporal Dementia , Corticobasal Degeneration Solutions , and the Alzheimer's Association . He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest.

Publisher Copyright:
© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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