Time between milestone events in the Alzheimer's disease amyloid cascade
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 cognitio...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | NeuroImage |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811920311617 |
| _version_ | 1828925973172584448 |
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| author | Philip S. Insel Michael C. Donohue David Berron Oskar Hansson Niklas Mattsson-Carlgren |
| author_facet | Philip S. Insel Michael C. Donohue David Berron Oskar Hansson Niklas Mattsson-Carlgren |
| author_sort | Philip S. Insel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T23:24:28Z |
| format | Article |
| id | doaj.art-9878de3bc0db4ad7841e564627490a1d |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-13T23:24:28Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-9878de3bc0db4ad7841e564627490a1d2022-12-21T23:27:35ZengElsevierNeuroImage1095-95722021-02-01227117676Time between milestone events in the Alzheimer's disease amyloid cascadePhilip S. Insel0Michael C. Donohue1David Berron2Oskar Hansson3Niklas Mattsson-Carlgren4Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, United States; Corresponding authors at: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, United StatesClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Memory Clinic, Skåne University Hospital, Malmö, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden; Corresponding authors at: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.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.http://www.sciencedirect.com/science/article/pii/S1053811920311617Alzheimer's diseaseβ-amyloidTau PETCognition |
| spellingShingle | Philip S. Insel Michael C. Donohue David Berron Oskar Hansson Niklas Mattsson-Carlgren Time between milestone events in the Alzheimer's disease amyloid cascade NeuroImage Alzheimer's disease β-amyloid Tau PET Cognition |
| title | Time between milestone events in the Alzheimer's disease amyloid cascade |
| title_full | Time between milestone events in the Alzheimer's disease amyloid cascade |
| title_fullStr | Time between milestone events in the Alzheimer's disease amyloid cascade |
| title_full_unstemmed | Time between milestone events in the Alzheimer's disease amyloid cascade |
| title_short | Time between milestone events in the Alzheimer's disease amyloid cascade |
| title_sort | time between milestone events in the alzheimer s disease amyloid cascade |
| topic | Alzheimer's disease β-amyloid Tau PET Cognition |
| url | http://www.sciencedirect.com/science/article/pii/S1053811920311617 |
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