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Time between milestone events in the Alzheimer's disease amyloid cascade

Insel, Philip S. LU ; Donohue, Michael C. ; Berron, David LU ; Hansson, Oskar LU orcid and Mattsson-Carlgren, Niklas LU orcid (2021) In NeuroImage 227.
Abstract

Objective: Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease. Methods: In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Results: Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7–8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4–5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4–6 years before Aβ-positivity. Conclusions: Increases in tau and cognitive dysfunction occur... (More)

Objective: Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease. Methods: In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Results: Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7–8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4–5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4–6 years before Aβ-positivity. Conclusions: Increases in tau and cognitive dysfunction occur years before commonly used thresholds for Aβ-positivity. Explicit estimates of the time for these events provide a clearer picture of the time-course of the amyloid cascade and identify potential windows for specific treatments.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Cognition, Tau PET, β-amyloid
in
NeuroImage
volume
227
article number
117676
publisher
Elsevier
external identifiers
  • pmid:33359337
  • scopus:85098718371
ISSN
1053-8119
DOI
10.1016/j.neuroimage.2020.117676
language
English
LU publication?
yes
id
525ba4f8-8ed1-4d5b-bc42-6542da1eb2f7
date added to LUP
2021-01-13 09:39:18
date last changed
2024-09-06 12:03:05
@article{525ba4f8-8ed1-4d5b-bc42-6542da1eb2f7,
  abstract     = {{<p>Objective: Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease. Methods: In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Results: Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7–8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4–5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4–6 years before Aβ-positivity. Conclusions: Increases in tau and cognitive dysfunction occur years before commonly used thresholds for Aβ-positivity. Explicit estimates of the time for these events provide a clearer picture of the time-course of the amyloid cascade and identify potential windows for specific treatments.</p>}},
  author       = {{Insel, Philip S. and Donohue, Michael C. and Berron, David and Hansson, Oskar and Mattsson-Carlgren, Niklas}},
  issn         = {{1053-8119}},
  keywords     = {{Alzheimer's disease; Cognition; Tau PET; β-amyloid}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{NeuroImage}},
  title        = {{Time between milestone events in the Alzheimer's disease amyloid cascade}},
  url          = {{http://dx.doi.org/10.1016/j.neuroimage.2020.117676}},
  doi          = {{10.1016/j.neuroimage.2020.117676}},
  volume       = {{227}},
  year         = {{2021}},
}