APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging.
APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging.
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DOI：
10.1002/ana.21843
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发表时间：
2010-01
影响因子：
11.2
通讯作者：
Mintun, Mark A.
中科院分区：
文献类型：
--
作者：
Morris, John C.;Roe, Catherine M.;Xiong, Chengjie;Fagan, Anne M.;Goate, Alison M.;Holtzman, David M.;Mintun, Mark A.
研究载脂蛋白E（APOE）基因型与年龄的相互作用，以及与认知正常老化的临床前阿尔茨海默病（AD）体内指标的相互作用。241名年龄在45岁至88岁之间的认知功能正常的人，用匹兹堡化合物B（PIB）进行了脑淀粉样蛋白成像研究。在241例患者中，168例（70%）还进行了淀粉样β 42（Aβ42）、tau和磷酸化tau（ptau 181）的脑脊液（CSF）检测。所有个体均进行APOE基因分型。PIB平均皮质结合电位（MCBP）升高的个体频率以年龄依赖性方式从45-49岁的0%上升到80-88岁的30.3%。与MCBP升高相比，CSF Aβ42水平降低似乎开始更早（45-49岁人群中的18.2%），并以更高的频率随年龄增加（80-88岁时为50%）。APOE 4基因型存在基因剂量效应，随着APOE 4等位基因数量的增加，MCBP升高幅度更大，CSF Aβ42降低幅度更大。携带APOE 2等位基因的个体MCBP未随年龄增加，CSF Aβ42水平高于不携带APOE 2等位基因的个体。APOE 4或APOE 2对CSF tau或ptau 181无影响。随着年龄的增长，大脑Aβ沉积增加是APOE 4的病理生物学表型。检测Aβ沉积的生物标志物序列可能首先是CSF Aβ42降低，然后是PIB的MCBP升高。相当大比例的认知正常个体具有推定的临床前AD。
To examine interactions of Apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer’s disease (AD) in cognitively normal aging. Two hundred and 41 cognitively normal individuals, age 45 to 88 years, had cerebral amyloid imaging studies with Pittsburgh Compound-B (PIB). Of the 241 individuals, 168 (70%) also had cerebrospinal fluid (CSF) assays of amyloid-beta42 (Aβ42), tau, and phosphorylated tau (ptau181). All individuals were genotyped for APOE. The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age-dependent manner from 0% at ages 45-49 years to 30.3% at 80-88 years. Reduced levels of CSF Aβ42 appear to begin earlier (18.2% of those age 45-49 years) and increase with age in higher frequencies (50% at age 80-88 years) than elevations of MCBP. There is a gene dose effect for the APOE4 genotype, with greater MCBP increases and greater reductions in CSF Aβ42 with increased numbers of APOE4 alleles. Individuals with an APOE2 have no increase in MCBP with age and have higher CSF Aβ42 levels than individuals without an APOE2 allele. There is no APOE4 or APOE2 effect on CSF tau or ptau181. Increasing cerebral Aβ deposition with age is the pathobiological phenotype of APOE4. The biomarker sequence that detects Aβ deposition may first be lowered CSF Aβ42, followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
11
作者：
Gustafson, Deborah R.;Skoog, Ingmar;Blennow, Kaj
通讯作者：
Blennow, Kaj
影响因子：
6.1
作者：
Fagan, AM;Watson, M;Holtzman, DM
通讯作者：
Holtzman, DM
影响因子：
9.9
作者：
Bretsky, P;Guralnik, JM;Seeman, TE
通讯作者：
Seeman, TE
影响因子：
2.6
作者：
Coats, M;Morris, JC
通讯作者：
Morris, JC