Modified amyloid variants in pathological subgroups of β-amyloidosis.
Modified amyloid variants in pathological subgroups of β-amyloidosis.
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DOI：
10.1002/acn3.577
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发表时间：
2018-07
影响因子：
5.3
通讯作者：
Walter J
中科院分区：
文献类型：
--
作者：
Gerth J;Kumar S;Rijal Upadhaya A;Ghebremedhin E;von Arnim CAF;Thal DR;Walter J
β淀粉样蛋白（Aβ）在斑块中的沉积和脑淀粉样血管病（CAA）是阿尔茨海默病（AD）的共同特征。斑块中经修饰的Aβ的连续沉积表征了Aβ成熟的不同生化阶段。然而，CAA中血管Aβ沉积物的分子组成及其与斑块的关系仍然是个谜。对24例对照、27例病理学定义的临床前AD和20例症状性AD病例的内侧颞叶和枕叶中的焦磷酸化和磷酸化Aβ的血管和实质沉积物进行化学分析。CAA中Aβ的连续沉积类似于斑块中Aβ的成熟，并使CAA的三个生化阶段得以区分。B‐CAA 1期的特征为在不存在焦氨基化Aβ N3 pE和磷酸化Aβ pS 8的情况下Aβ沉积。B-CAA 2期显示额外的Aβ N3 pE，B-CAA 3期显示额外的Aβ pS 8。根据CAA和斑块中Aβ成熟分期，可将Aβ病理分为3组：CAA中Aβ成熟晚期组; CAA和斑块中Aβ成熟相等组;斑块中Aβ成熟晚期组。所有症状性AD病例均表现为终末期斑块成熟，而CAA可表现为未成熟Aβ沉积。值得注意的是，Aβ病理学组1与动脉高血压相关，组2与痴呆的发展相关。CAA和斑块中Aβ成熟的平衡定义了β淀粉样变性的不同病理亚组。鉴别诊断和治疗干预应考虑CAA相关Aβ成熟与认知功能下降的相关性、CAA和斑块病理对定义的Aβ病理亚组中痴呆发生的个体贡献以及与动脉高血压的亚组相关性。
Amyloid β (Aβ) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post‐translationally modified Aβ in plaques characterizes distinct biochemical stages of Aβ maturation. However, the molecular composition of vascular Aβ deposits in CAA and its relation to plaques remain enigmatic. Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated Aβ in the medial temporal and occipital lobe of 24 controls, 27 pathologically‐defined preclinical AD, and 20 symptomatic AD cases. Sequential deposition of Aβ in CAA resembled Aβ maturation in plaques and enabled the distinction of three biochemical stages of CAA. B‐CAA stage 1 was characterized by deposition of Aβ in the absence of pyroglutaminated Aβ N3pE and phosphorylated Aβ pS8. B‐CAA stage 2 showed additional Aβ N3pE and B‐CAA stage 3 additional Aβ pS8. Based on the Aβ maturation staging in CAA and plaques, three case groups for Aβ pathology could be distinguished: group 1 with advanced Aβ maturation in CAA; group 2 with equal Aβ maturation in CAA and plaques; group 3 with advanced Aβ maturation in plaques. All symptomatic AD cases presented with end‐stage plaque maturation, whereas CAA could exhibit immature Aβ deposits. Notably, Aβ pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia. Balance of Aβ maturation in CAA and plaques defines distinct pathological subgroups of β‐amyloidosis. The association of CAA‐related Aβ maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined Aβ pathology subgroups, and the subgroup‐related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.
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影响因子：
7.1
作者：
Balakrishnan K;Rijal Upadhaya A;Steinmetz J;Reichwald J;Abramowski D;Fändrich M;Kumar S;Yamaguchi H;Walter J;Staufenbiel M;Thal DR
通讯作者：
Thal DR
DOI：
10.1006/bbrc.2000.3490
发表时间：
2000-09-24
影响因子：
3.1
作者：
Harigaya, Y;Saido, TC;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
4.2
作者：
Ball, M;Braak, H;Khachaturian, Z
通讯作者：
Khachaturian, Z
影响因子：
6
作者：
Held, Friederike;Morris, Alan W. J.;Schreiber, Stefanie
通讯作者：
Schreiber, Stefanie
影响因子：
7.1
作者：
Antonios G;Saiepour N;Bouter Y;Richard BC;Paetau A;Verkkoniemi-Ahola A;Lannfelt L;Ingelsson M;Kovacs GG;Pillot T;Wirths O;Bayer TA
通讯作者：
Bayer TA