Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome.
Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome.
复制标题
患有唐氏综合症的成年人的母亲患阿尔茨海默病的风险增加。
DOI：
10.1016/s0140-6736(94)91398-6
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Mayeux,R
中科院分区：
文献类型：
--
作者：
Schupf,N;Kapell,D;Lee,JH;Ottman,R;Mayeux,R
大多数患有唐氏综合症(DS)的成年人在40岁前发展为阿尔茨海默病(AD)的神经病理学特征。DS中的大多数非连接事件是母体起源的。因此，我们推测，DS和AD的共同遗传易感性将与DS患者母亲中AD频率的增加有关，但与父亲中的AD频率无关。我们进一步假设，共同的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。96名患有DS的成年人和80名其他形式的精神发育迟滞的成年人的家庭通过纽约州发育障碍服务网络进行了确认。半结构化访谈被用来获得关于父母是否存在非中风相关性痴呆和其他障碍的信息。与对照母亲相比，DS先证者母亲患痴呆的风险增加(风险比2·6[95%CI 0 9~7·3])。出生时年龄在35岁或以下的母亲患痴呆症的风险是对照组母亲的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患者的父亲和对照组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的影响。患有DS的成年母亲的痴呆症的家庭聚集性支持了DS和AD共同遗传易感性的假设。
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% Cl 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.