Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain
Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain
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DOI：
10.1007/s00401-003-0783-1
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发表时间：
2004-01-01
影响因子：
12.7
通讯作者：
McGeer, PL
中科院分区：
文献类型：
--
作者：
Akiyama, H;Kondo, H;McGeer, PL
家族性英国痴呆（FBD）的神经病理学特征是一种独特的淀粉样蛋白ABri沉积。它是前体蛋白BRI的一种异常形式的片段。在FBD中，由于阻止识别正常停止密码子的点突变，BRI被拉长了11个氨基酸。我们研究了正常BRI在非fbd病例中的表达。针对BRI序列提出了三种抗体，并用于免疫印迹和免疫组织化学。每一种抗体通过Western blotting检测到约35kda的条带。在人死后脑组织中，在神经元细胞质中检测到细小颗粒状的BRI。海马CA3和CA4的锥体神经元以及小脑皮层的浦肯野细胞的BRI染色最为强烈。这种强烈表达BRI的神经元分布与报道的FBD患者中ABri沉积的发生相似。病理病例中，在老年斑的营养不良神经突、缺血病例的病变周围、小脑的鱼雷和葡萄糖变化、路易神经突、气球状神经元以及缺氧病例中普遍存在的神经元中检测到BRI。这些结果表明，BRI在神经元过程中转运，并可能参与神经末梢的某些作用。虽然BRI在大脑中的生理作用仍有待确定，但BRI在各种脑病变中的行为似乎与淀粉样蛋白前体蛋白的行为有些相似，淀粉样蛋白是阿尔茨海默病β -淀粉样蛋白的来源。
Familial British dementia (FBD) is characterized neuropathologically by deposition of a unique amyloid-forming protein, ABri. It is a fragment of an abnormal form of a precursor protein, BRI. In FBD, BRI is elongated by 11 amino acids due to a point mutation that prevents recognition of the normal stop codon. We have investigated the expression of normal BRI in non-FBD cases. Three antibodies were raised against sequences of BRI and were used for immunoblotting and immunohistochemistry. Each of these antibodies detected a band at approximately 35 kDa by Western blotting. In postmortem human brain tissues, BRI was detected as fine granules in the neuronal cytoplasm. Pyramidal neurons in CA3 and CA4 of the hippocampus as well as Purkinje cells in the cerebellar cortex were most intensely stained for BRI. Such a distribution of neurons strongly expressing BRI parallels the reported occurrence of ABri deposits in patients with FBD. In pathological cases, BRI was detected in dystrophic neurites in senile plaques, around lesions in ischemic cases, in torpedo and glumose changes in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in hypoxic cases. These results suggest that BRI is transported in neuronal processes and is possibly involved in some role in nerve terminals. While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein, which is the source of the beta-amyloid protein of Alzheimer's disease.