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

• Published in: NeuroImage (Orlando, Fla.) Vol. 227; p. 117676
• Main Authors: Insel, Philip S., Donohue, Michael C., Berron, David, Hansson, Oskar, Mattsson-Carlgren, Niklas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-02-2021; Elsevier Limited; Elsevier
• Subjects: Aged; Alzheimer Disease - complications; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Biomarkers; Cerebrospinal fluid; Clinical Medicine; Cognition; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Dementia; Disease Progression; Female; Humans; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Memory; Neurodegenerative diseases; Neurologi; Neurology; Pathology; Positron-Emission Tomography; Regions; Tau PET; Tau protein; tau Proteins - metabolism; Time Factors; β-amyloid; Cognition; Tau PET; Alzheimer's disease; β-amyloid
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2020.117676

•The time-from-Aβ pathology measure identifies early signs of disease progression.•Increases in tau pathology and cognitive dysfunction occur 4–8 years prior to Aβ-positivity.•Slowing the spread of tau pathology and cognitive decline may require treatment prior to significant Aβ pathology.
Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease.
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.
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.
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.