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 使人衰弱，是老年人最常见的肌肉疾病（超过 60 岁）。 s-IBM 的一个有趣的方面是它的肌纤维 表型与阿尔茨海默病的特征非常相似 (AD) 大脑（“IBM-AD 表型”），包括以下物质的异常积累： β-淀粉样蛋白前体蛋白 (betaAPP) 和其他几种蛋白 累积在 AD 大脑中。与 AD 的另一个相似之处是存在 遗传形式，称为“遗传性包涵体肌病（h-IBM）”， 其临床表现早于 s-IBM，但具有肌肉- 纤维表型与相同，但显然不太先进 比 s-IBM 的。与 AD 大脑类似，异常的肌纤维 s-和 h-IBM 肌肉，体内和体外。因此，我们建议 betaAPP 过度表达（整个分子和/或 Abeta 片段） 老年（s-IBM）或遗传异常成人（h-IBM）肌肉的环境 纤维引起分子扰动，导致 IBM 特定的 空泡肌纤维变性和 IBM-AD 的表达 表型。该提案涉及时间表，因此 致病级联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 利用 s-IBM 肌肉培养物的模型；和 cc) 诱导模型 利用成熟的培养正常人体肌肉纤维 转移betaAPP基因； 2）诱导的体内老年大鼠模型 基于将 betaAPP 基因转移到老年大鼠腓肠肌中 肌肉。抗氧化治疗，包括雌激素，将在 异常培养物。我们假设体内衰老涉及 组织可能是 AD 组和 AD 组的诱发因素。 IBM 的，尤其是每种形式的零星、更常见的形式。因为 我们的人体组织自发和诱导模型培养类型 患者的实际受影响无法用于研究大脑 参与AD，可能我们的结果可能会提供其他信息- 无法获得与发病机制和治疗相关的信息 AD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.