人类演化与阿尔茨海默病：免疫受体CD33的独特作用
大多数脊椎动物在无法再繁殖时死亡，但人类是个例外，具有较长的生育后寿命。老年人对后代照顾、觅食和传递生态文化知识有贡献，但认知能力的衰退会削弱这些益处并增加社会成本。研究发现，与阿尔茨海默病关联的免疫受体CD33的一个等位基因在人类中独特且保护性，类似于黑猩猩的功能状态，可能有助于抵消因人类特定大脑演化导致的交互作用改变。其他几个例子表明，某些衍生等位基因可以保护人类免受年龄相关认知退化的疾病，如神经退行性疾病或脑血管不足。选择性适应可能强到足以支持特定保护认知衰退的等位基因，以最大化生育后个体对年轻亲属的贡献。
摘要：
The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer's dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer's disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin.
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