Additional file 4: Figure S4. of Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway

Cell death was not induced in this study. (A) MTS assay was used for checking cell viability under simvastatin, 3MA and/or bafilomycin treated condition. N = 5 experiments. (PDF 57 kb

Additional file 1: Figure S1. of Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway

Statins regulate cholesterol levels in astrocytes. (A) Cellular cholesterol levels were measured by filipin staining. MβCD is a positive control. (B) Quantitative analysis of Figure S1A using the Image J program (N = 3 experiments). ** p < 0.01, *** p < 0.001 vs. vehicle-treated cells. (PDF 217 kb

Additional file 2: Figure S2. of Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway

Fluvastatin induces IDE secretion from astrocytes. (A) Increased IDE levels secreted from the primary astrocytes by fluvastatin in a concentration-dependent manner. Blots are representative of at least 3 independent experiments (N = 3 experiments). (B) Quantitative analysis of Figure S2A. ** p < 0.01 vs. vehicle-treated cells. (PDF 71 kb

Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease

<p>The secretion of proteins that lack a signal sequence to the extracellular milieu is regulated by their transition through the unconventional secretory pathway. IDE (insulin-degrading enzyme) is one of the major proteases of amyloid beta peptide (Aβ), a presumed causative molecule in Alzheimer disease (AD) pathogenesis. IDE acts in the extracellular space despite having no signal sequence, but the underlying mechanism of IDE secretion extracellularly is still unknown. In this study, we found that IDE levels were reduced in the cerebrospinal fluid (CSF) of patients with AD and in pathology-bearing AD-model mice. Since astrocytes are the main cell types for IDE secretion, astrocytes were treated with Aβ. Aβ increased the IDE levels in a time- and concentration-dependent manner. Moreover, IDE secretion was associated with an autophagy-based unconventional secretory pathway, and depended on the activity of RAB8A and GORASP (Golgi reassembly stacking protein). Finally, mice with global haploinsufficiency of an essential autophagy gene, showed decreased IDE levels in the CSF in response to an intracerebroventricular (i.c.v.) injection of Aβ. These results indicate that IDE is secreted from astrocytes through an autophagy-based unconventional secretory pathway in AD conditions, and that the regulation of autophagy is a potential therapeutic target in addressing Aβ pathology.</p

Additional file 2 of Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

is a table presenting demographic data of the complete study cohort. (DOCX 58 kb

Additional file 6: of Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

is a table presenting demographic data of young-middle-aged controls. (XLSX 10 kb