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Quantifying the pathophysiological timeline of Alzheimer's disease
Eric Yang1, Michael Farnum, Victor Lobanov
1Johnson and Johnson, PRDUS. Eyang3@its.jnj.com
Journal of Alzheimer'S Disease : JAD
|June 23, 2011
Summary
This study quantifies Alzheimer's disease (AD) progression by synchronizing biomarkers. Findings confirm a sequential pattern: reduced amyloid-beta (Aβ(42)) and brain atrophy precede elevated tau levels.
Area of Science:
- Neuroscience
- Biomarker Research
- Alzheimer's Disease Pathophysiology
Background:
- Alzheimer's disease (AD) progression models link clinical stages to biomarker changes (CSF, imaging, cognition).
- Quantifying continuous biomarker trajectories in clinical trials is challenging due to disease duration vs. trial length.
Purpose of the Study:
- To de-convolve AD progression trends and quantify timelines of pathophysiological changes.
- To synchronize cerebrospinal fluid (CSF) and imaging biomarkers with disease duration.
Main Methods:
- Developed a model to replicate ADAS-Cog 13 score progression, estimating disease duration and pathological stage.
- Synchronized CSF and imaging biomarkers based on the refined disease timeline.
- Analyzed biomarker dynamics to confirm and refine hypothetical AD progression models.
Main Results:
- Confirmed predictions of previous hypothetical AD progression models.
- Established concrete timelines for key pathobiological events in AD.
- Demonstrated a sequential pattern: decreased CSF Aβ(42) and brain atrophy precede increased CSF tau and phospho-tau.
Conclusions:
- Synchronization of biomarkers using ADAS-Cog 13 provides a precise timeline for AD progression.
- The study validates a specific sequence of biomarker changes critical for understanding AD pathophysiology.
- Findings support a distinct temporal order of amyloid-beta reduction, brain atrophy, and subsequent tau elevations.
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