Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer’s Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

在整个成年期和衰老过程中，我们的大脑会以类似于阿尔茨海默病 （AD） 中更快萎缩的平均模式经历结构损失。使用纵向成人寿命样本（30-89 岁;2-7 个时间点）和 AD 的四个多基因评分，我们表明 AD 敏感大脑特征的变化与健康成年人的遗传性 AD 风险和记忆力下降相关。我们首先显示遗传风险与早期 Braak 地区年龄比预期更多的脑损失有关，并发现这超出了 APOE 基因型。接下来，我们使用以年龄为条件的大脑变化轨迹，对来自阿尔茨海默病神经影像学计划的 AD 控制数据进行机器学习，以识别 AD 敏感特征并模拟它们在健康成年人中的变化。遗传 AD 风险与许多 AD 敏感特征的多变量变化有关，我们表明大多数 ~50 岁以上的个体在 AD 敏感区域处于加速脑损失的轨迹上。最后，与大脑变化较少的高遗传风险成年人相比，大脑变化较高的高遗传风险成年人在成年后表现出更多的记忆力下降。我们的研究结果表明，在健康个体中可以通过衰老和 AD 相关神经变的共同模式检测到定量的 AD 风险因素，该模式沿着连续体发生，并跟踪成年后的记忆力下降。