Time between milestone events in the Alzheimer's disease amyloid cascade
Insel, Philip S. LU ; Donohue, Michael C. ; Berron, David LU ; Hansson, Oskar LU
and Mattsson-Carlgren, Niklas
LU
(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.
(Less)
- author
- Insel, Philip S.
LU
; Donohue, Michael C.
; Berron, David
LU
; Hansson, Oskar
LU
and Mattsson-Carlgren, Niklas
LU
- organization
- publishing date
- 2021
- 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
-
- scopus:85098718371
- pmid:33359337
- 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
- 2024-09-20 13:16:00
@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}},
}