Intraneuronal Abeta immunoreactivity is not a predictor of brain amyloidosis-beta or neurofibrillary degeneration.
Intraneuronal Abeta immunoreactivity is not a predictor of brain amyloidosis-beta or neurofibrillary degeneration.
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DOI：
10.1007/s00401-006-0191-4
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发表时间：
2007-04
影响因子：
12.7
通讯作者：
Miller DL
中科院分区：
文献类型：
--
作者：
Wegiel J;Kuchna I;Nowicki K;Frackowiak J;Mazur-Kolecka B;Imaki H;Wegiel J;Mehta PD;Silverman WP;Reisberg B;Deleon M;Wisniewski T;Pirttilla T;Frey H;Lehtimäki T;Kivimäki T;Visser FE;Kamphorst W;Potempska A;Bolton D;Currie JR;Miller DL
在32名对照受试者、31名唐氏综合征患者和36名散发性阿尔茨海默病患者的脑中检测了神经元中的淀粉样蛋白β（Aβ）免疫反应性，以确定神经元内Aβ免疫反应性是否是导致纤维斑块形成和/或神经元变性的阿尔茨海默型病理学的早期表现。婴儿神经元中Aβ免疫反应性的出现以及儿童晚期、成年期和正常衰老期间大多数脑结构中稳定的神经元类型特异性Aβ免疫反应性不支持这一假设。在神经元中，Aβ 4-13 aa和8-17 aa的抗体不存在或仅检测到微量反应，表明神经元内Aβ主要是α和γ分泌酶的产物（Aβ17-40/42）。通过蛋白质印迹法证实对照脑中存在N端截短的Aβ17-40和Aβ17-42，并通过质谱法证实Aβ17-40的身份。神经元中α-和γ -分泌酶产物以及斑块中β-和γ-分泌酶产物的普遍存在，与神经元索马中检测到的Aβ免疫阳性物质对斑块中淀粉样蛋白存款的主要贡献相反。与更易受阿尔茨海默病型病理影响的区域相比，在对纤维状Aβ沉积、神经退行性变和神经元丢失易感性较低的结构中观察到最强的神经元内Aβ17-42免疫反应性。这些观察结果表明，在这项研究中检测到的神经元内Aβ免疫反应性不是脑淀粉样变性或神经退行性变的预测因子。在基本上整个生命周期中，无神经元病理的结构中Aβ免疫反应性水平恒定，表明神经元内氨基末端截短的Aβ代表正常神经元代谢的产物。
Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ17–40/42). The presence of N-terminally truncated Aβ17–40 and Aβ17–42 in the control brains was confirmed by Western blotting and the identity of Aβ17–40 was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ17–42 immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism.
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DOI：
10.1093/jnen/62.6.685
发表时间：
2003-06-01
影响因子：
3.2
作者：
Frackowiak, J;Miller, DL;Mazur-Kolecka, B
通讯作者：
Mazur-Kolecka, B
DOI：
10.1097/00005072-199411000-00011
发表时间：
1994-11-01
影响因子：
3.2
作者：
FRACKOWIAK, J;ZOLTOWSKA, A;WISNIEWSKI, HM
通讯作者：
WISNIEWSKI, HM
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
82.9
作者：
Hartmann, T;Bieger, SC;Beyreuther, K
通讯作者：
Beyreuther, K
影响因子：
2.9
作者：
Frackowiak, J;Sukontasup, T;Mazur-Kolecka, B
通讯作者：
Mazur-Kolecka, B