Alzheimer Centre Amsterdam, Amsterdam University Medical Centers, Amsterdam, Netherlands; Department of Neurology, Amsterdam University Medical Centers, Amsterdam, Netherlands; Life Science Partners, Amsterdam, Netherlands.
VIB Center for Brain and Disease Research, Leuven, Belgium; KU Leuven Department for Neurology, Leuven, Belgium; Dementia Research Institute, University College London, London, UK.
Lancet. 2021 Apr 24;397(10284):1577-1590. doi: 10.1016/S0140-6736(20)32205-4. Epub 2021 Mar 2.
In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer's disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.
在本次研讨会上，我们重点介绍了阿尔茨海默病领域的主要进展。最新数据表明，到 2050 年，欧洲痴呆症的患病率将翻一番，全球患病率将增加两倍，而根据阿尔茨海默病的生物学（而非临床）定义，这一估计值要高出 3 倍。阿尔茨海默病的最早阶段（细胞阶段）与淀粉样蛋白 β 的积累平行发生，导致 tau 病理的扩散。阿尔茨海默病的风险有 60-80%取决于遗传因素，目前已经确定了 40 多个与阿尔茨海默病相关的遗传风险位点，其中 APOE 等位基因与该疾病的相关性最强。新型生物标志物包括淀粉样蛋白 β 和磷酸化 tau 的 PET 扫描和血浆检测，它们在临床和研究应用中显示出巨大的潜力。基于多领域生活方式的预防试验表明，认知风险增加的参与者有认知益处。生活方式因素不会直接影响阿尔茨海默病的病理，但仍能为患有阿尔茨海默病的个体带来积极的结果。有前景的药物治疗已处于临床试验的后期阶段，包括抗淀粉样蛋白 β、抗 tau 和抗炎策略。
