Date of download: 9/17/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid Arch Neurol. 2009;66(4): doi: /archneurol Sortilin-related receptor SorLA/LR11 (LR11) was secreted into culture medium from SH-SY5Y cells and into cerebrospinal fluid (CSF) in human brain. A, Western blot of approximately 250-kD LR11 band in SH-SY5Y cell lysates was slightly larger than the secreted LR11 band found in conditioned media. B, Secreted LR11 band in CSF in human brain is similarly slightly smaller than the LR11 membrane fraction band (lysis buffer extract). Figure Legend:

Date of download: 9/17/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid Arch Neurol. 2009;66(4): doi: /archneurol Stability of sortilin-related receptor SorLA/LR11 (LR11) in cerebrospinal fluid (CSF) of patients with Alzheimer disease (AD). A, Western blot showed LR11, secretase-cleaved soluble β-amyloid precursor protein (sAPP), and apolipoprotein E (ApoE) band densities in CSF from a group of patients with AD having lumbar samples repeated after 6 months. The LR11, sAPP, and ApoE levels were highly stable between baseline and subsequent CSF draws. There were no significant differences between first and second CSF levels of LR11 (P =.81), α-secretase–cleaved APP (sAPPα) (P =.80), β-secretase–cleaved APP (sAPPβ) (P =.78), or ApoE (P =.65). Baseline and final CSF levels of LR11 (P <.001, r = 0.92 [B]), sAPPα (P <.001, r = 0.97 [C]), sAPPβ (P =.001, r = 0.72 [D]), and ApoE (P =.001, r = 0.78 [E]) significantly correlated with each other. OD indicates optical density. Figure Legend:

Date of download: 9/17/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid Arch Neurol. 2009;66(4): doi: /archneurol The sortilin-related receptor SorLA/LR11 (LR11) and secretase-cleaved soluble β-amyloid precursor protein (sAPP) levels in cerebrospinal fluid in patients with early Alzheimer disease (AD) were significantly decreased and correlated with the sAPP level but not the apolipoprotein (ApoE) level. A, Western blot showed that levels of LR11, α-secretase–cleaved APP (sAPPα), and β- secretase–cleaved (sAPPβ) significantly decreased in patients having early AD compared with control subjects (CTRLs), while the ApoE level did not show significant changes. β-Actin demonstrated the consistency with equal protein loading. B, Densitometric quantitation of LR11 from A confirmed a difference between patients with AD and CTRLs (P =.03). C, Densitometric quantitation of sAPPβ from A showed that sAPPβ was reduced in patients with AD compared with CTRLs (P =.02). D, Densitometric quantitation of ApoE from A showed that there was no difference in ApoE levels between patients with AD and CTRLs (P =.56). E, The LR11 level significantly correlated with sAPPβ level (P <.001, r =0.72). F, The LR11 level did not correlate with ApoE level (P =.46, r = 0.15). B- F, Open circle indicates CTRLs; solid circle, patients with AD; and OD, optical density. Figure Legend:

Date of download: 9/17/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid Arch Neurol. 2009;66(4): doi: /archneurol Combining predictors for classification using the area under the receiver operating characteristic (ROC) curve. A, Univariate β42- amyloid (Aβ42) ROC curve with bivariate (LR11 and Aβ42) ROC curve overlain. Adding LR11 to the discriminant function with Aβ42 improved sensitivity and specificity (area under the ROC curve changes from to 0.865, P =.01). B, Univariate Aβ42 ROC curve with bivariate (phosphorylated [P] tau and Aβ42) ROC curve overlain. Adding P-tau did not improve sensitivity and specificity (area under the ROC curve changes from to 0.793). Figure Legend:

Date of download: 9/17/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid Arch Neurol. 2009;66(4): doi: /archneurol The sortilin-related receptor SorLA/LR11 (LR11) levels but not apolipoprotein E (ApoE) levels in postmortem cerebrospinal fluid samples from patients with autopsy-confirmed Alzheimer disease (AD) were significantly decreased. A, Western blot showed that the LR11 level was significantly decreased in patients with AD compared with healthy control subjects (CTRLs) or CTRLs with non- AD dementias (others); ApoE did not show significant differences. Roman numerals after AD indicate Braak stage. B, Densitometric quantification of LR11 from A confirmed a significant difference between patients with AD and healthy CTRLs or others (P.05). OD indicates optical density. Figure Legend: