Dwyer Barney E, Stone Meghan L, Zhu Xiongwei, Perry George, Smith Mark A
Research Service (151), VA Medical & Regional Office Center, White River Junction, VT 05009, USA.
J Biomed Biotechnol. 2006;2006(3):24038. doi: 10.1155/JBB/2006/24038.
Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity of genes encoding enzymes of the heme biosynthesis pathway to genetic loci linked to sporadic, late-onset AD. In addition, we suggest that identification of individuals carrying the genetic trait for acute porphyria may provide a unique resource for investigating AD pathogenesis and inform treatment and management decisions.
阿尔茨海默病（AD）是一种致命的神经退行性疾病，其致病机制尚不清楚。最近的重要数据表明，神经元血红素缺乏可能与AD的发病机制有关。如果这是真的，导致细胞内血红素缺乏的因素可能会改变AD的病程。卟啉症是一种代谢紊乱疾病，其特征是血红素生物合成途径中的酶缺乏。我们假设，患有急性肝卟啉症遗传特征的个体，其AD可能有显著差异。我们详细阐述了这一假设，并简要回顾了可能与AD相关的急性肝卟啉症的特征。我们注意到，血红素生物合成途径中编码酶的基因与散发性晚发性AD相关的基因座接近。此外，我们建议，识别携带急性卟啉症遗传特征的个体，可能为研究AD发病机制提供独特资源，并为治疗和管理决策提供参考。
