Alzheimer's disease as a multistage process: an analysis from a population-based cohort study

Aging
Silvan LicherM Kamran Ikram

Abstract

In cancer research, multistage models are used to assess the multistep process that leads to the onset of cancer. In view of biological and clinical similarities between cancer and dementia, we used these models to study Alzheimer's disease (AD). From the population-based Rotterdam Study, we included 9,362 non-demented participants, of whom 1,124 developed AD during up to 26 years of follow-up. Under a multistage model, we regressed the logarithm of AD incidence rate against the logarithm of five-year age categories. The slope in this model reflects the number of steps (n-1) required for disease onset before the final step leading to disease manifestation. A linear relationship between log incidence rate and log age was observed, with a slope of 12.82 (95% confidence interval: 9.01-16.62), equivalent to 14 steps. We observed fewer steps for those at high genetically determined risk: 12 steps for APOE-ε4 carriers, and 10 steps for those at highest genetic risk based on APOE and a genetic risk score. The pathogenesis of AD complies with a multistage disease-model, requiring 14 steps before disease manifestation. Genetically predisposed individuals require fewer steps indicating that they already inherited multiple of these steps....Continue Reading

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Citations

May 6, 2020·European Journal of Epidemiology·M Arfan IkramTrudy Voortman
Nov 5, 2020·Scientific Reports·Daniela GerovskaMarcos J Araúzo-Bravo
Jun 22, 2021·Journal of Alzheimer's Disease : JAD·Igor AkushevichAnatoliy I Yashin
Mar 26, 2021·Current Alzheimer Research·Luoyu WangZhongxiang Ding

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Methods Mentioned

BETA
protein folding
genotyping
chips

Software Mentioned

Minimac
R
SPSS
CRAN

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