ALZHEIMER LIKE PATHOLOGY IN INCLUSION BODY MYOPATHY

散发性包涵体肌炎(S-IBM)是一种进行性、高度 衰弱，老年人最常见的肌肉疾病(超过 60岁)。S-ibm一个耐人寻味的方面是它的肌肉纤维 表型特征与阿尔茨海默病非常相似 (Ad)脑(“IBM-AD表型”)，包括异常堆积的： β-淀粉样前体蛋白(β-APP)和其他几种蛋白 在阿尔茨海默病脑内蓄积。与AD的另一个相似之处是存在 遗传性形式，称为“遗传性包涵体肌病(h-IBM)”， 临床表现早于S-ibm，但有肌肉- 纤维表型相同，尽管明显不那么高级 而不是S--国际商用机器公司。类似于阿尔茨海默病的大脑，异常的肌肉纤维 S-和h-IBM肌肉，体内和体外。因此，我们建议 BetaAPP过表达(全分子和/或Abeta片段在 老年(S-ibm)或遗传异常成人(h-ibm)肌肉的环境 纤维会引起分子干扰，导致IBM特有的 空泡性肌纤维变性与IBM-AD的表达 表型。这项提案涉及时间表，因此 致病级联反应早期步骤的可能机制。它 涉及：1)三种长期体外模型，即a)自发的 利用S-IBM肌肉培养的模型；以及cc)诱导模型 利用成熟的培养的正常人类肌肉纤维制成 转移βAPP基因；2)体内诱导衰老大鼠模型 将β-APP基因导入老龄大鼠腓肠肌的研究 肌肉。抗氧化治疗，包括雌激素，将在 反常的文化。我们推测，在体内涉及的衰老 组织可能是AD组和AD患者的易感因素(S) IBM的，尤其是以每种形式的零星的、更常见的形式。因为 我们这类人体组织的自发和诱导培养模型 实际上在患者身上并不能用来研究大脑 参与AD‘s，我们的结果可能会提供相反的- 无法获得与该病的发病机制和治疗相关的信息 广告公司的。

Sporadic inclusion-body myositis (s-IBM) is a progressive, highly debilitating, and the most common muscle disease of older persons (over age 60). An intriguing aspect of s-IBM is that its muscle fiber phenotype has features remarkably similar to those of Alzheimer Disease (AD) brain ("IBM-AD phenotype"), including abnormal accumulations of: beta-amyloid precursor protein (betaAPP) and of several other proteins accumulated in AD brain. Another similarity to AD is the presence of hereditary forms, termed "hereditary inclusion-body myopathies (h-IBM)", which clinically are manifest earlier than s-IBM, but have a muscle- fiber phenotype identical to, though apparently somewhat less advanced than, that of s-IBM. Similarly to AD brain, abnormal muscle fibers of s- and h-IBM muscle, in vivo and in vitro. Therefore, we propose that betaAPP over-expression (whole molecule and/or Abeta fragment in the milieu of aged (s-IBM) or genetically-abnormal adult (h-IBM) muscle fibers causes molecular disturbances leading to the IBM-specific vacuolar muscle-fiber degeneration and expression of the IBM-AD phenotype. This proposal addresses the schedule, and therefore the possible mechanisms, of the early steps in the pathogenic cascade. It involves: 1) three long-term in vitro models, namely, a) spontaneous model utilizing cultures of s-IBM muscle; and cc) an induced model utilizing matured cultured normal human muscle fibers into which is transferred the betaAPP gene; and 2) an induced in vivo aged-rat model based on transfer of the betaAPP gene into aged-rat gastrocnemius muscle. Anti-oxidant treatments, including estrogens, will be done on abnormal cultures. We postulate that in vivo aging of the involve tissues may be a predisposing factor(s) in both the AD group and the IBM's, especially in the sporadic, more common, forms of each. Because our type of cultured spontaneous and induced models of the human tissue actually affected in the patient are not available to study brain involvement in the AD's, possibly our results may provide otherwise- unavailable information relevant to the pathogenesis and treatment of the AD's.