Four distinct trajectories of tau deposition identified in Alzheimer's disease

Jacob W Vogel; Alexandra L Young; Neil P Oxtoby; Ruben Smith; Rik Ossenkoppele; Olof T Strandberg; Renaud La Joie; Leon M Aksman; Michel J Grothe; Yasser Iturria-Medina; Michael J Pontecorvo; Michael D Devous; Gil D Rabinovici; Daniel C Alexander; Chul Hyoung Lyoo; Alan C Evans; Oskar Hansson; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1038/s41591-021-01309-6

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Four distinct trajectories of tau deposition identified in Alzheimer's disease

Journal article

Open access

Peer reviewed

Four distinct trajectories of tau deposition identified in Alzheimer's disease

Jacob W Vogel, Alexandra L Young, Neil P Oxtoby, Ruben Smith, Rik Ossenkoppele, Olof T Strandberg, Renaud La Joie, Leon M Aksman, Michel J Grothe, Yasser Iturria-Medina, …

Nature medicine, Vol.27(5), pp.871-881

05/2021

DOI: 10.1038/s41591-021-01309-6

PMCID: PMC8686688

PMID: 33927414

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https://research.vumc.nl/en/publications/18cdbd26-e980-4a7f-8981-bb23804a08f8View

Open Access

Abstract

Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.

Phenotype

Aged

Alzheimer Disease - classification

Alzheimer Disease - pathology

Carbolines - pharmacology

Cerebral Cortex - diagnostic imaging

Cerebral Cortex - pathology

Cognitive Dysfunction - pathology

Female

Humans

Male

Neuroimaging - methods

Positron-Emission Tomography - methods

Radiopharmaceuticals - administration & dosage

Spatio-Temporal Analysis

tau Proteins - metabolism

Details

Title: Subtitle: Four distinct trajectories of tau deposition identified in Alzheimer's disease
Creators: Jacob W Vogel - Montreal Neurological Institute and Hospital
Alexandra L Young - King's College London
Neil P Oxtoby - University College London
Ruben Smith - Skåne University Hospital
Rik Ossenkoppele - Amsterdam Neuroscience
Olof T Strandberg - Lund University
Renaud La Joie - University of California, San Francisco
Leon M Aksman - University College London
Michel J Grothe - Hospital Universitario Virgen del Rocío
Yasser Iturria-Medina - Montreal Neurological Institute and Hospital
Michael J Pontecorvo - Avid Radiopharmaceuticals
Michael D Devous - Avid Radiopharmaceuticals
Gil D Rabinovici - University of California, San Francisco
Daniel C Alexander - University College London
Chul Hyoung Lyoo - Gangnam Severance Hospital
Alan C Evans - Montreal Neurological Institute and Hospital
Oskar Hansson - Lund University
Alzheimer’s Disease Neuroimaging Initiative
Contributors: HyungSub Shim (Contributor) - University of Iowa, Neurology
Resource Type: Journal article
Publication Details: Nature medicine, Vol.27(5), pp.871-881
DOI: 10.1038/s41591-021-01309-6
PMID: 33927414
PMCID: PMC8686688
NLM abbreviation: Nat Med
ISSN: 1078-8956
eISSN: 1546-170X
Grant note: Department of Health MR/S03546X/1 / Medical Research Council K99 AG065501 / NIA NIH HHS R01 AG045611 / NIA NIH HHS CIHR P01 AG019724 / NIA NIH HHS T32 MH019112 / NIMH NIH HHS MR/T027800/1 / Medical Research Council U01 AG024904 / NIA NIH HHS P50 AG023501 / NIA NIH HHS
Language: English
Date published: 05/2021
Academic Unit: Neurology; Psychiatry
Record Identifier: 9984302201702771

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