Description
We have found that C99 is highly localized at MAMs. C99 is one of products of APP processed by beta-secretase and is downregulated by gamma-secretase, generating beta-amyloid. Our data indicates that elevated levels of C99 correlate with the dysregulation of cholesterol and sphingolipid regulation (Pera et al., 2017). We are currently researching how C99 contributes to the regulation of lipid homeostasis, and how the alteration in the level of C99 in MAMs plays a role in the pathogenesis of AD.
Representative electron micrographs of ER apposed to mitochondria (M) (i.e. MAM) in fibroblasts from a control subject, an FAD patient, and an SAD patient. Note the unusually large area of apposition in the FAD patient, extending for more than 1000 nm (arrowheads). (Area-Gomez et al., 2012)