Gispert J D, Rami L, Sánchez-Benavides G, Falcon C, Tucholka A, Rojas S, Molinuevo J L
Clinical and Neuroimaging Departments, Barcelonabeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Neurobiol Aging. 2015 Oct;36(10):2687-701. doi: 10.1016/j.neurobiolaging.2015.06.027. Epub 2015 Jul 8.
The progression of Alzheimer's disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subject's level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele.
阿尔茨海默病（AD）的进展特征是脑萎缩的复杂轨迹，其受到年龄和载脂蛋白E等位基因ε4（APOE4）状态相互作用的影响。在本文中，我们报告了以AD-脑脊液（CSF）指数为代表的疾病全生物学谱中灰质的非线性体积变化。该指数反映了受试者的病理水平以及在AD连续体中的位置。我们还评估了APOE4基因型的相关影响。与AD-CSF指数相关的萎缩模式高度对称，与典型的AD特征相符。内侧颞叶结构在疾病进展过程中表现出不同的萎缩动态。双侧海马旁皮质以及从中颞叶延伸至缘上回的顶颞区域体积最初增加，随后恢复。同样，楔前叶的一部分与AD-CSF指数呈现出相当线性的负相关，而其他一些簇直到指数值对应于脑脊液tau蛋白阳性值时才显示出明显萎缩。APOE4携带者随着AD进展海马体积减少更为明显。总体而言，所报告的萎缩模式与先前研究结果中提到的模式密切一致。然而，检测到的非线性表明在AD进展的特定时刻可能发生了不同的病理过程，并揭示了APOE4等位基因的影响。
