近日，英国卡迪夫大学Julie Williams等研究人员提出了在阿尔茨海默氏病的遗传复合模型。该论文于2020年2月28日在线发表于《自然—神经科学》。

Title: The multiplex model of the genetics of Alzheimer’s disease

Author: Rebecca Sims, Matthew Hill, Julie Williams

Issue&Volume: 2020-02-28

Abstract: Genes play a strong role in Alzheimer’s disease (AD), with late-onset AD showing heritability of 58–79% and early-onset AD showing over 90%. Genetic association provides a robust platform to build our understanding of the etiology of this complex disease. Over 50 loci are now implicated for AD, suggesting that AD is a disease of multiple components, as supported by pathway analyses (immunity, endocytosis, cholesterol transport, ubiquitination, amyloid-β and tau processing). Over 50% of late-onset AD heritability has been captured, allowing researchers to calculate the accumulation of AD genetic risk through polygenic risk scores. A polygenic risk score predicts disease with up to 90% accuracy and is an exciting tool in our research armory that could allow selection of those with high polygenic risk scores for clinical trials and precision medicine. It could also allow cellular modelling of the combined risk. Here we propose the multiplex model as a new perspective from which to understand AD. The multiplex model reflects the combination of some, or all, of these model components (genetic and environmental), in a tissue-specific manner, to trigger or sustain a disease cascade, which ultimately results in the cell and synaptic loss observed in AD.

DOI: 10.1038/s41593-020-0599-5

Source: https://www.nature.com/articles/s41593-020-0599-5