Dysferlin is a newly identified binding partner of AβPP and it co-aggregates with amyloid-β42 within sporadic inclusion-body myositis (s-IBM) muscle fibers

Excerpt

Dysferlin is a 237 kDa type II trans-membrane protein involved in plasmalemmal repair and resealing after injury, and in T-tubule construction and calcium homeostasis [reviewed in 2]. Although in skeletal and cardiac muscle dysferlin is localized mainly to plasmalemma and cytoplasmic vesicles, recently, it was also localized to T-tubules and other myofiber structures [2]. DYSF gene mutations cause three main clinical phenotypes of autosomal recessive myopathies, called dysferlinopathies [2]. Unlike normal human muscle biopsies in which dysferlin is immunohistochemically present in the muscle fiber sarcolemma, in dysferlinopathies, dysferlin is absent from the sarcolemma, and is either absent or prominently reduced per immunoblots of muscle biopsies and monocytes [2, 5]. Beyond muscle diseases, in Alzheimer disease (AD) brain, dysferlin was abnormally accumulated in dystrophic neurites within amyloid-β (Aβ) plaques [6]. …