哥伦比亚大学研究人员发现，某些携带阿尔茨海默病高风险基因APOE ε4的人之所以能够保持心智敏锐直到80多岁，关键在于他们拥有一种罕见的FN1基因突变1。这项研究表明，该突变通过限制纤维连接蛋白在脑血管周围的积累，从而保护血脑屏障免受损伤1。
约五分之一的人携带APOE ε4基因变异，这是阿尔茨海默病最强的常见遗传风险因素1。研究人员发现，携带APOE ε4的实验小鼠脑内纤维连接蛋白含量几乎是携带APOE ε3小鼠的两倍1。这种过量的纤维连接蛋白通过激活整合素和焦点粘着激酶的异常信号，破坏血脑屏障的完整性1。相关研究已发表在《Nature Aging》2026年第6卷第1901页1。
这项发现揭示了纤维连接蛋白如何导致大脑损伤，为开发针对携带高风险基因者的特异性治疗方法提供了新的科学方向1。
Researchers at Columbia University have identified a rare genetic mutation in the FN1 gene that allows some individuals carrying the APOE ε4 gene—the strongest common genetic risk factor for Alzheimer's disease—to maintain cognitive sharpness well into their eighties.1 The protective mechanism involves a variant that limits the accumulation of fibronectin around cerebral blood vessels, thereby shielding the blood-brain barrier from damage.1 Approximately one in five people carry the APOE ε4 variation.1
The study, published in Nature Aging in September 2026, reveals how excess fibronectin disrupts the blood-brain barrier through abnormal signaling involving integrins and focal adhesion kinase.1 In mice carrying APOE ε4, brain fibronectin levels were nearly double those found in mice with APOE ε3.1 This discovery offers new directions for developing targeted therapeutic approaches to combat Alzheimer's disease. According to researcher Caghan Kizil, "This research allows us to move from genetic clues to disease mechanisms."1
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