Corder E H, Robertson K, Lannfelt L, Bogdanovic N, Eggertsen G, Wilkins J, Hall C
Genetic Epidemiology, Odense University, Denmark.
Nat Med. 1998 Oct;4(10):1182-4. doi: 10.1038/2677.
HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines that are also implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-), respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+) subjects were demented (30% compared with 15%) or had peripheral neuropathy (70% compared with 39%) at least once, and they had threefold more symptomatic examinations (13% compared with 3% and 42% compared with 14%, respectively)(P < 0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an etiologic risk factor. Long-term survivors of HIV infection with E4 may be at high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.
人类免疫缺陷病毒(HIV)会引发中枢神经系统的慢性病毒感染,导致慢性神经胶质细胞激活以及神经胶质细胞因子的过度表达,而这些因子也与阿尔茨海默病(AD)的发病机制有关。AD的一个遗传风险因素是载脂蛋白E(APOE)的E4亚型。在此,我们比较了HIV队列中具有和不具有E4亚型(分别为E4(+)和E4(-))的受试者出现神经症状的频率。与E4(-)受试者相比,E4(+)受试者出现痴呆(分别为30%和15%)或至少一次出现周围神经病变(分别为70%和39%)的人数是前者的两倍,并且他们出现症状性检查的次数是前者的三倍(分别为13%和3%以及42%和14%)(P < 0.0001)。因此,HIV感染和AD的神经症状通过一个病因风险因素联系在一起。携带E4的HIV感染长期存活者可能患AD的风险很高;反之,基因-病毒相互作用可能会加速AD的发病进程。