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Alzheimer's disease as a multistage process: an analysis from a population-based cohort study
Silvan Licher1, Kimberly D van der Willik1,2, Elisabeth J Vinke1,3
1Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
Aging
|February 28, 2019
Summary
Alzheimer's disease (AD) pathogenesis involves 14 multistage steps. Genetic predisposition, such as APOE-ε4, reduces these steps, suggesting inherited risk factors contribute to AD development.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Multistage models are crucial for understanding cancer development.
- Alzheimer's disease (AD) shares biological and clinical similarities with cancer.
- These similarities suggest the applicability of multistage models to AD research.
Purpose of the Study:
- To investigate Alzheimer's disease (AD) pathogenesis using multistage models.
- To determine the number of steps involved in AD onset.
- To explore the impact of genetic risk factors on the number of disease steps.
Main Methods:
- Utilized data from the population-based Rotterdam Study (9,362 participants).
- Applied multistage modeling to analyze AD incidence rates over up to 26 years of follow-up.
- Regressed the logarithm of AD incidence rate against age categories to estimate disease steps.
Main Results:
- A significant linear relationship was observed between log incidence rate and log age, indicating 14 steps in AD pathogenesis.
- Individuals with high genetic risk (APOE-ε4 carriers) showed fewer steps (12 steps).
- Those with the highest genetic risk (APOE and genetic risk score) required even fewer steps (10 steps).
Conclusions:
- Alzheimer's disease (AD) pathogenesis follows a multistage model with an estimated 14 steps.
- Genetic predisposition significantly reduces the number of steps required for AD manifestation.
- Identifying these steps is vital for developing effective intervention strategies for AD.