PT -期刊文章盟Philip s . Insel盟Atul Kumar AU -奥斯卡·汉森盟Niklas Mattsson-Carlgren AU -阿尔茨海默病的神经影像学的TI -遗传适度β-Amyloid协会的认知和MRI在阿尔茨海默病大脑结构- 10.1212 / WNL援助。0000000000207305 DP - 2023 7月04 TA -神经病半岛投注体育官网学PG - e20 e29 //www.ebmtp.com/content/101/1/e20.short VI - 101 IP - 1 4099 - 4100 - //www.ebmtp.com/content/101/1/e20.full所以Neurology2023 7月04;101 AB -背景和目标之间的关系有很大的异质性增加β-amyloid (Aβ)病理学和早期认知功能障碍临床前阿尔茨海默病(AD)。在这个阶段,有些人没有认知功能障碍的迹象,而其他人则显示明显下滑的迹象。解释这个异质性因素尤为重要对于理解发展的广告,但在很大程度上仍未知。在这项研究中,我们对一组遗传变异可能影响Aβ之间的关系,大脑结构和认知表现在两大军团。方法2953种抗体治疗的认知没有参与者在无症状的阿尔茨海默病(A4)的研究中,基因变异之间的相互作用和18 f-florbetapir宠物标准摄入值比率(SUVR)预测临床前阿尔茨海默症的认知复合(扣带皮层部位)进行评估。A4研究中所确定的遗传变异在阿尔茨海默病神经影像学评估(ADNI, N = 527)与纵向认知和脑萎缩认知未受损伤的参与者和那些患有轻度认知障碍。结果在A4的研究中,4个基因变异显著放缓Aβ负载和认知之间的关系。小等位基因的变异与额外的扣带皮层部位分数的减少增加有关AβSUVR (rs78021285,β=−2.29 = 0.40,pFDR = 0.02,最近的基因ARPP21;rs71567499,β=−2.16 = 0.38,pFDR = 0.02,最近的基因PPARD;,β=−1.68 rs10974405 SE = 0.29,最近的基因GLIS3 pFDR = 0.02)。 The minor allele of rs7825645 was associated with less decrease in PACC scores with increasing Aβ SUVR (β = 0.71, SE = 0.13, pFDR = 0.04, nearest gene FGF20). The genetic variant rs76366637, in linkage disequilibrium with rs78021285, was available in both the A4 and ADNI. In the A4, rs76366637 was strongly associated with reduced PACC scores with increasing Aβ SUVR (β = −1.01, SE = 0.21, t = −4.90, p < 0.001). In the ADNI, rs76366637 was associated with accelerated cognitive decline (χ2 = 15.3, p = 0.004) and atrophy over time (χ2 = 26.8, p < 0.001), with increasing Aβ SUVR.Discussion Patterns of increased cognitive dysfunction and accelerated atrophy due to specific genetic variation may explain some of the heterogeneity in cognition in preclinical and prodromal AD. The genetic variant near ARPP21 associated with lower cognitive scores in the A4 and accelerated cognitive decline and brain atrophy in the ADNI may help to identify those at the highest risk of accelerated progression of AD.A4=Anti-Amyloid Treatment in Asymptomatic Alzheimer disease; Aβ=β-amyloid; AD=Alzheimer disease; ADNI=Alzheimer Disease Neuroimaging Initiative; CU=cognitively unimpaired; ES=effect size; FDR=false discovery rate; GV=genetic variant; HWE=Hardy-Weinberg equilibrium; LD=linkage disequilibrium; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; PACC=Preclinical Alzheimer Cognitive Composite; SUVR=standardized uptake value ratio; WMH=white matter hyperintensity

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