Amylin deposition in the brain: A second amyloid in Alzheimer disease?
Amylin deposition in the brain: A second amyloid in Alzheimer disease?
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DOI：
10.1002/ana.23956
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发表时间：
2013-10
影响因子：
11.2
通讯作者：
Despa, Florin
中科院分区：
文献类型：
--
作者：
Jackson, Kaleena;Barisone, Gustavo A.;Diaz, Elva;Jin, Lee-way;DeCarli, Charles;Despa, Florin
高淀粉血症是肥胖和胰岛素抵抗患者常见的胰腺疾病，已知会导致胰岛淀粉蛋白寡聚和细胞毒性，导致β细胞大量耗尽和2型糖尿病的发生。最近的数据显示，高淀粉血症还会影响血管系统、心脏和肾脏。因此，我们假设寡聚化的胰淀素可能在糖尿病患者的脑血管系统和脑实质中积聚。用实时定量聚合酶链式反应、免疫组织化学、免疫印迹和酶联免疫吸附试验检测糖尿病伴血管性痴呆或阿尔茨海默病(AD)患者、非糖尿病AD患者和年龄匹配的健康对照组的脑内胰淀素积聚。在糖尿病患者的颞叶灰质中发现了胰淀素寡聚体和斑块，但没有发现对照组。此外，在血管和血管周围可见广泛的淀粉素沉积。有趣的是，在临床上没有明显糖尿病的晚发性AD患者的血管和脑实质中也发现了淀粉素沉积。偶见胰淀素和A-β混合沉积。然而，淀粉蛋白的积累导致淀粉样蛋白的形成，而不依赖于Aβ的沉积。胰淀素渗入的组织表现为间质间隙增大，空泡化，海绵状改变，毛细血管在胰淀素积聚部位弯曲。与胰腺不同的是，没有证据表明大脑中有胰淀素合成。代谢紊乱和衰老促进了淀粉样蛋白在脑血管系统和灰质中的积累，改变了微血管和组织结构。脑血管壁上淀粉样蛋白的形成也可能导致Aβ不能从脑中清除，从而导致AD的发病。
Hyperamylinemia, a common pancreatic disorder in obese and insulin resistant patients, is known to cause amylin oligmerization and cytotoxicity in pancreatic islets leading to β-cell mass depletion and development of type-2 diabetes. Recent data revealed that hyperamylinemia also affects the vascular system, heart and kidneys. We, therefore, hypothesized that oligomerized amylin might accumulate in cerebrovascular system and brain parenchyma of diabetic patients. Amylin accumulation in the brain of diabetic patients with vascular dementia or Alzheimer’s disease (AD), non-diabetic patients with AD, and age-matched healthy controls was assessed by quantitative real-time PCR, immunohistochemistry, western blot and ELISA. Amylin oligomers and plaques were identified in the temporal lobe gray matter from diabetic patients, but not controls. In addition, extensive amylin deposition was found in blood vessels and perivascular spaces. Intriguingly, amylin deposition was also detected in blood vessels and brain parenchyma of patients with late-onset AD without clinically apparent diabetes. Mixed amylin and Aβ deposits were occasionally observed. However, amylin accumulation leads to amyloid formation independent of Aβ deposition. Tissues infiltrated by amylin show increased interstitial space, vacuolation, spongiform change, and capillaries bended at amylin accumulation sites. Unlike the pancreas, there was no evidence of amylin synthesis in the brain. Metabolic disorders and aging promote accumulation of amylin amyloid in cerebrovascular system and gray matter altering microvasculature and tissue structure. Amylin amyloid formation in the wall of cerebral blood vessels may also induce failure of elimination of Aβ from the brain, thus contributing to the etiology of AD.
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影响因子：
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作者：
Craft, Suzanne
通讯作者：
Craft, Suzanne
影响因子：
4.2
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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