Johnson K H, Sletten K, Hayden D W, O'Brien T D, Roertgen K E, Westermark P
Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
Am J Pathol. 1992 Nov;141(5):1013-9.
The N-terminus of a mutant form of apolipoprotein AI [apoAI] has previously been shown to be the subunit protein of amyloid fibrils in a human kindred with a form of familial amyloid polyneuropathy (FAP, type III) and in a recently reported kindred with a form of non-neuropathic hereditary amyloidosis. In this study, we demonstrate by amino-acid sequence analysis, that a form of vascular amyloidosis occurring in the lungs of aged dogs is derived from a N-terminal fragment of apoAI and that no amino acid substitution is present in this confirmed sequence. This represents the first documentation of apoAI as a precursor for a form of amyloidosis in animals, and provides the first documentation of apoAI as a precursor for amyloid fibrils in a form of age-associated ("senile") amyloidosis. Secondary structure prediction analysis of the N-terminal regions of normal human and dog apoAI indicated a propensity for beta-pleated sheet conformation, and thus amyloidogenesis, in 40 and 45% of the respective sequences. These results suggest that apoAI (like transthyretin) may serve as an amyloid precursor protein for both familial and senile forms of amyloidosis. ApoAI should, therefore, be considered as a potential amyloid precursor when forms of human senile amyloidosis of unknown origin are evaluated.
载脂蛋白AI [apoAI]突变形式的N端先前已被证明是患有某种家族性淀粉样多神经病（III型家族性淀粉样多神经病，FAP）的人类家族以及最近报道的患有某种非神经性遗传性淀粉样变性家族中淀粉样纤维的亚基蛋白。在本研究中，我们通过氨基酸序列分析证明，老年犬肺中出现的一种血管淀粉样变性源自apoAI的N端片段，且在该已确认序列中不存在氨基酸取代。这是apoAI作为动物中一种淀粉样变性的前体的首次记录，并提供了apoAI作为与年龄相关（“老年性”）淀粉样变性形式中淀粉样纤维前体的首次记录。对正常人和犬apoAI N端区域的二级结构预测分析表明，各自序列中分别有40%和45%的序列倾向于形成β折叠构象，从而易于发生淀粉样变。这些结果表明，apoAI（如转甲状腺素蛋白）可能是家族性和老年性淀粉样变性形式的淀粉样前体蛋白。因此，在评估不明来源的人类老年性淀粉样变性形式时，应将apoAI视为潜在的淀粉样前体。
