Akiyama Haruhiko, Kondo Hiromi, Arai Tetsuaki, Ikeda Kenji, Kato Masanori, Iseki Eizo, Schwab Claudia, McGeer Patrick L
Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585, Tokyo, Japan.
Acta Neuropathol. 2004 Jan;107(1):53-8. doi: 10.1007/s00401-003-0783-1. Epub 2003 Oct 29.
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.
家族性英国型痴呆（FBD）的神经病理学特征是一种独特的淀粉样蛋白形成蛋白ABri的沉积。它是前体蛋白BRI异常形式的一个片段。在FBD中，由于一个点突变阻止了正常终止密码子的识别，BRI延长了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的序列制备了三种抗体，并用于免疫印迹和免疫组织化学。通过蛋白质印迹法，这些抗体中的每一种都在大约35 kDa处检测到一条带。在死后的人脑组织中，BRI在神经元细胞质中被检测为细颗粒。海马体CA3和CA4区的锥体细胞以及小脑皮质的浦肯野细胞对BRI的染色最为强烈。这种强烈表达BRI的神经元分布与FBD患者中报道的ABri沉积物的出现情况相似。在病理情况下，在老年斑中的营养不良性神经突、缺血病例病变周围、小脑中的鱼雷样和颗粒样改变、路易小体神经突、气球样神经元以及一般缺氧病例中的神经元中都检测到了BRI。这些结果表明，BRI在神经元突起中运输，并且可能在神经末梢中发挥某种作用。虽然BRI在大脑中的生理作用尚待确定，但BRI在各种脑病变中的行为似乎与淀粉样前体蛋白有些类似，淀粉样前体蛋白是阿尔茨海默病β淀粉样蛋白的来源。
