Schupf N, Kapell D, Lee J H, Ottman R, Mayeux R
Laboratory of Epidemiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Lancet. 1994 Aug 6;344(8919):353-6. doi: 10.1016/s0140-6736(94)91398-6.
Most adults with Down's syndrome (DS) develop neuropathology characteristic of Alzheimer's disease (AD) by the age of 40. Most of the non-dysjunction events in DS are of maternal origin. We postulated therefore that a shared genetic susceptibility to DS and AD would be associated with an increased frequency of AD among mothers, but not fathers, of individuals with DS. We further hypothesised that the shared susceptibility could involve an accelerated ageing process, leading to the birth of a child with DS to a relatively young mother and to an increased risk of dementia in the mother and her relatives. Families of 96 adults with DS and of 80 adults with other forms of mental retardation were ascertained through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. There was an increase in risk of dementia among mothers of DS probands compared with control mothers (risk ratio 2.6 [95% CI 0.9-7.3]). The risk of dementia among mothers who were 35 or younger when their DS children were born was 5 times that of control mothers (4.9 [1.6-15.4]). There was no increase in risk of dementia among mothers who were older (> 35 years) at the proband's birth (0.8 [0.2-3.4]). There was no difference in risk of dementia between fathers of DS cases and fathers of controls (1.2 [0.4-3.9]) and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD.
大多数唐氏综合征（DS）成年患者在40岁时会出现阿尔茨海默病（AD）的神经病理学特征。DS中的大多数非分离事件源自母亲。因此，我们推测，DS和AD的共同遗传易感性与DS患者的母亲（而非父亲）患AD的频率增加有关。我们进一步假设，这种共同易感性可能涉及加速衰老过程，导致相对年轻的母亲生下患有DS的孩子，并增加母亲及其亲属患痴呆症的风险。通过纽约州发育障碍服务网络确定了96名患有DS的成年患者和80名患有其他形式智力障碍的成年患者的家庭。采用半结构化访谈获取父母中是否存在与非中风相关的痴呆症和其他疾病的信息。与对照母亲相比，DS先证者的母亲患痴呆症的风险增加（风险比2.6 [95%可信区间0.9 - 7.3]）。DS孩子出生时年龄在35岁及以下的母亲患痴呆症的风险是对照母亲的5倍（4.9 [1.6 - 15.4]）。先证者出生时年龄较大（> 35岁）的母亲患痴呆症的风险没有增加（0.8 [0.2 - 3.4]）。DS患者的父亲与对照患者的父亲患痴呆症的风险没有差异（1.2 [0.4 - 3.9]），年龄对这种风险没有明显影响。DS成年患者母亲中痴呆症的家族聚集支持了DS和AD存在共同遗传易感性的假设。
