Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
复制标题
DOI：
10.1371/journal.pone.0060747
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Lampert EJ;Roy Choudhury K;Hostage CA;Petrella JR;Doraiswamy PM;Alzheimer’s Disease Neuroimaging Initiative
阳性家族史(FH)是晚发性阿尔茨海默病(AD)的危险因素。我们的目的是研究FH对认知光谱中病理和神经元丢失生物标记物的影响。对来自国家生物标志物研究的数据进行横断面分析。阿尔茨海默病神经成像倡议国家研究。257名受试者(年龄55-89岁)，分为认知正常(CN)组、轻度认知障碍(MCI)组和AD组，进行脑脊液和FH检查。脑脊液Aβ42、tau及tau/Aβ42比值，磁共振测量海马区体积。单变量和多变量分析。MCI组FH+组脑脊液Aβ42低于FH组(p = .005)，t-tau高于FH组(p = =0.02)，t-tau/Aβ42比值高于FH组(p = =0.002)。在校正载脂蛋白E4后，FH对MCI的病理标记物仍有显著的残留作用(p<；0.05)。在CN组中，47%的FH+患者表现为“AD的病理特征”(csf t-tau/Aβ_(42)比值为0.39)，而FH−对照组为21%(p = =0.03)。在AD患者中，FH效应不明显。FH+和FH−受试者之间的海马体和颅内体积在任何一组中都没有差异。晚发性AD阳性家族史与MCI患者脑β淀粉样蛋白和tau蛋白表型异常的发生率较高有关。家族史中无法解释的遗传遗传性大约是载脂蛋白E4效应的一半。有必要进行纵向研究，以便更明确地研究这一问题。
A positive family history (FH) is a risk factor for late-onset Alzheimer’s disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum. Cross-sectional analyses of data from a national biomarker study. The Alzheimer’s Disease Neuroimaging Initiative national study. 257 subjects (ages 55–89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes. Univariate and multivariate analyses. In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH− subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited “pathologic signature of AD” (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH− controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH− subjects in any group. A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.
登录
查看更多内容
影响因子：
9.9
作者：
Honea, R. A.;Swerdlow, R. H.;Burns, J. M.
通讯作者：
Burns, J. M.
DOI：
10.1073/pnas.0705036104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Mosconi, Lisa;Brys, Miroslaw;de Leon, Mony J.
通讯作者：
de Leon, Mony J.
影响因子：
--
作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
通讯作者：
Rosand, Jonathan
影响因子：
9.9
作者：
Honea, Robyn A.;Swerdlow, Russell H.;Burns, Jeffrey M.
通讯作者：
Burns, Jeffrey M.
DOI：
10.1093/brain/awp007
发表时间：
2009-04
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Schuff N;Woerner N;Boreta L;Kornfield T;Shaw LM;Trojanowski JQ;Thompson PM;Jack CR Jr;Weiner MW;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative