阿尔茨海默病高危人群的灰质体积、代谢减退和β-淀粉样蛋白的区域性模式。

Regional patterns of gray matter volume, hypometabolism, and beta-amyloid in groups at risk of Alzheimer's disease.

机构信息

Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Boulevard H. Becquerel, Caen, France; Normandie Université, UNICAEN, PSL Research University, EPHE, Inserm, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany.

Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Boulevard H. Becquerel, Caen, France; Normandie Université, UNICAEN, PSL Research University, EPHE, Inserm, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

出版信息

Neurobiol Aging. 2018 Mar;63:140-151. doi: 10.1016/j.neurobiolaging.2017.10.023. Epub 2017 Nov 7.

Abstract

Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly carriers of the apolipoprotein E ε4 (APOE4, n = 17), patients with subjective cognitive decline (n = 16), and patients with mild cognitive impairment (n = 30), head-to-head intermodality comparisons were performed on cross-sectional structural magnetic resonance images as well as 18F-fluorodeoxyglucose and 18F-florbetapir positron emission tomography scans. In mild cognitive impairment patients, 3 distinct biomarker patterns were recovered, similarly seen in AD patients: (1) in medial temporal regions, local GMV reduction exceeded hypometabolism, (2) in temporoparietal regions, hypometabolism predominated over GMV reduction, and (3) in frontal regions, Aβ deposition exceeded GMV reduction and hypometabolism. In subjective cognitive decline patients, only pattern 1 was detected, while APOE4 carriers demonstrated only pattern 3. Our findings highlight that regional AD-like biomarker patterns may vary across different at-risk populations, potentially reflecting differential mediators of these risks.

摘要

阿尔茨海默病(AD)的特征是β-淀粉样蛋白(Aβ)沉积和神经退行性变。为了寻找这些病理的迹象,我们比较了三组 AD 风险人群的局部生物标志物程度和 Aβ沉积、葡萄糖代谢低下和灰质体积(GMV)减少的模式。在载脂蛋白 E ε4(APOE4,n=17)的老年携带者、有主观认知减退(n=16)的患者和有轻度认知障碍(n=30)的患者中,对横断面结构磁共振成像以及 18F-氟脱氧葡萄糖和 18F-氟比他滨正电子发射断层扫描进行了跨模态比较。在轻度认知障碍患者中,恢复了三种不同的生物标志物模式,与 AD 患者相似:(1)在颞叶内侧区域,局部 GMV 减少超过代谢低下,(2)在颞顶叶区域,代谢低下超过 GMV 减少,(3)在额叶区域,Aβ沉积超过 GMV 减少和代谢低下。在主观认知减退患者中,仅检测到模式 1,而 APOE4 携带者仅表现出模式 3。我们的研究结果表明,局部 AD 样生物标志物模式可能在不同的高危人群中有所不同,这可能反映了这些风险的不同中介因素。

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