Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.
Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2015.12.004
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发表时间：
2016-03
影响因子：
4.2
通讯作者：
Goldberg, Terry E.
中科院分区：
文献类型：
--
作者：
Gomar, Jesus J.;Conejero-Goldberg, Concepcion;Huey, Edward D.;Davies, Peter;Goldberg, Terry E.
由于年龄和/或遗传因素（即APOE基因）导致的代偿性神经生物学机制的妥协可能会影响BDNF val 66 met多态性对颞叶形态计量学和记忆性能的影响。我们研究了来自ADNI的两个队列：175名健康受试者和222名前驱和确诊AD受试者。在3年的随访中，每年进行结构MRI和认知性能评估。两个队列具有相似的BDNF瓦尔/瓦尔和Met等位基因携带者（包括瓦尔/Met和Met/Met个体）分布。在健康受试者中，与APOE E4携带者中的瓦尔纯合子相比，Met携带者中检测到后扣带回和楔前叶皮质变薄的显著趋势，分别具有大和中等效应量。MCI/AD队列显示，与APOE E4携带者中的瓦尔/瓦尔相比，BDNF Met携带者中的内嗅厚度纵向下降，效应量范围从中等到大。此外，在APOE E4阳性受试者中发现BDNF基因型对情景记忆（逻辑记忆和ADAS-Cog）和语义流畅性测量的影响，Met携带者在所有情况下表现更差。这些发现表明，在健康和病理老化中，APOE E4携带者中的BDNF Met携带者缺乏代偿机制。
Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e. APOE gene) may influence BDNF val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied two cohorts from ADNI: 175 healthy subjects and 222 with prodromal and established AD. Yearly structural MRI and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers’ (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices were detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes respectively. The MCI/AD cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. Also an effect of BDNF genotype was found in APOE E4 positive subjects for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers in APOE E4 carriers in healthy and pathological aging.
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DOI：
10.1016/j.jalz.2013.11.009
发表时间：
2014-11
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Gomar JJ;Conejero-Goldberg C;Davies P;Goldberg TE;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
2.6
作者：
Goldberg, Terry E.;Iudicello, Jennifer;Weinberger, Daniel R.
通讯作者：
Weinberger, Daniel R.
DOI：
10.1093/brain/awp123
发表时间：
2009-08
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Desikan RS;Cabral HJ;Hess CP;Dillon WP;Glastonbury CM;Weiner MW;Schmansky NJ;Greve DN;Salat DH;Buckner RL;Fischl B;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
3.7
作者：
Honea RA;Cruchaga C;Perea RD;Saykin AJ;Burns JM;Weinberger DR;Goate AM;Alzheimer’s Disease Neuroimaging Initiative (ADNI)
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
影响因子：
--
作者：
Gomar, Jesus J.;Bobes-Bascaran, Maria T.;Goldberg, Terry E.
通讯作者：
Goldberg, Terry E.