IDENTIFYING PHENOTYPES FOR PROTECTIVE GENES AGAINST ALZHEIMERS DISEASE

遗传因素在某些非典型形式的VERY中被证明 早发性阿尔茨海默病(AD)和家族聚集性 在临床确诊的一系列AD先证者中反复发现。 然而，极晚发病(75+)的家庭因素的存在 年)AD，这种疾病最常见的表现形式，主要是 未知。来自先前遗传流行病学调查的一些证据 而我们中心最近未公布的数据表明， 阿尔茨海默病的遗传度与先证者的AD发病年龄有关。 然而，到目前为止，对AD病例的几项研究并没有一致地发现 亲属罹患AD样原发性进行性痴呆症的风险 (PPD)与AD先证者的发病年龄有关。这个 以前研究的不一致可能在一定程度上归因于 小的先证者样本和调查策略 相对粗鲁。此外，包括在大多数国家的先驱 之前发表的调查是通过以下方式确定的 临床环境。这种确定方法将倾向于产生样品 有偏向早发年龄的AD患者，可能包括 有阳性家族史的先证者数量不成比例。这个 山体之间的密切联系。西奈医学院与犹太人 老年之家和医院(JHHA)提供学习的机会 极晚发型和早发型AD的家族性特征 先证者使用家族史评估技术。招聘 CORE将转介所有JHHA入院患者和精神病老年患者 山上的诊所。西奈，埃尔姆赫斯特，弗吉尼亚州布朗克斯生产一口井- 可能患有阿尔茨海默病的先证者，非阿尔茨海默病先证者， 认知完好的非常年长的对照组(来自JHHA人群) 进行家族史评估。毫不含糊的 转诊患者的痴呆症配偶，通过家人进行评估 告密者，也将接受评估。累积风险与年龄 产后呼吸暂停综合征的特定危险率-反映了 较高寿命-将在可能的AD先证者中进行评估，这些先证者具有不同的 关于设定的时间和对照组，有助于澄清发病的作用 产后抑郁的家族性风险。慢性阻塞性肺疾病患者的检查 神经病理学证实的阿尔茨海默病将消除一个错误来源， 风险估计中先证者的诊断错误分类。 不同地点之间和不同地点之间可能存在的家族史状况偏见 尸检和未尸检的AD先证者也将被检查。

Genetic factors have been demonstrated in certain atypical forms of very early onset Alzheimer's disease (AD) and familial aggregation has been repeatedly found in clinically identified series of AD probands. Nevertheless, the presence of familial factors in very late onset (75+ years) AD, the most commonly manifested form of the illness, is largely unknown. Some evidence from previous genetic epidemiological investion and recent unpublished data from our center suggest that the degree of heritability of AD is associated wit the AD onset age in the proband. Yet several studies of AD cases have not, to date, consistently found that the risk of relatives for an AD-like primary progressive dementia (PPD) is associated with the age at onset in the AD proband. The inconsistencies in previous studies may ell be in part attributable to small proband samples and investigative strategies that have been relatively crude. Furthermore, the probands included in most of the previously published investigations have been ascertained through clinical settings. This ascertainment method will tend to yield samples of AD patients biased toward an early onset age and may include a disproportionate number of probands with a positive family history. The close association between Mt. Sinai School of Medicine and the Jewish Home and Hospital for the Age (JHHA) offers the opportunity to study the familial characteristics of both very late onset AD and earlier onset AD probands using family history assessment techniques. The recruitment core will refer all JHHA admissions and those in the psychogeriatric clinics of the Mt. Sinai, Elmhurst, Bronx VA yielding a well- characterized sample of probable AD probands, non-AD demented probands, and cognitively intact very elderly controls (from the JHHA population) for family history assessment. The families of unambiguously non- demented spouses of the referred patients, assessed through family informants, will also be evaluated. The cumulative risks and the age specific hazard rate of PPD-reflecting the patterns of incidence over the late lifespan- will be assessed in probable AD probands with different on set times and comparison groups, helping to clarify the role of onset in familial risk of PPD. The examination of patients with neuropathologically confirmed AD will eliminated one source of error, diagnostic misclassification of the proband, in the risk estimates. Possible biases for family history status between sites and between autopsied and non-autopsied probable AD probands will also be examined.