Fig 1: Correlation of CSF lysosomal cathepsin levels with p‐tau181 across cohorts. (A) Correlation between p‐tau181 and individual lysosomal protease levels, grouped by protease family, in CSF in patients with symptomatic AD (Emory ADRC) or healthy aging adults (BrANCH). The levels were measured by SomaScan (SOMA) and TMT:MS (TMT) for most lysosomal proteases. (B) Sample correlations (CTSB and CTSL) from the Emory ADRC dataset. Alzheimer's disease patient samples are in red; control patients are in blue. (C) Sample correlation (CTSB and CTSD) from BrANCH data set. (Emory ADRC n = 160 AD patients, n = 140 healthy controls. UCSF BrANCH. n = 51.). ADRC: Alzheimer's Disease Resource Center, BrANCH: Brain Aging Network for Cognitive Health, CSF: Cerebrospinal fluid, CTSB: cathepsin B, CTSD: cathepsin D, CTSF: cathepsin F, CTSG: cathepsin G, CTSK: cathepsin K, CTSL: cathepsin L, CTSO: cathepsin O, CTSS: cathepsin S, CTSV: cathepsin V, CTSZ: cathepsin X/Z/P, LGMN: legumain (AEP), TMT:MS, Tandem Mass Tag Mass Spectrometry.
Fig 2: Impact of phosphorylation on cleavage of tau FRET peptides and tau recombinant varies by individual lysosomal protease. (A–D) Cleavage of FRET peptides pairs (Thr181, Ser199, Thr205, Thr217) across a pH range (4.0–6.0) by individual lysosomal proteases. Maximum slopes were derived from traces normalized to 0%–100% of minimum–maximum fluorescence; representative traces of the pH extremes are shown in insets. If a trace did not reach asymptote by end of time course, a maximum slope was not calculated. N = 3. (E) Summary of cleavage properties of individual lysosomal proteases and FRET peptide pairs. (F) Western blot showing time course of phosphorylated (p‐tau) and nonphosphorylated tau (tau) by cathepsin B (top) or cathepsin L (bottom) at pH 4.0 or pH 6.0. Representative of three replicates. AEP: Asparagine Endopeptidase, CTSB: cathepsin B, CTSD: cathepsin D, CTSF: cathepsin F, CTSG: cathepsin G, CTSK: cathepsin K, CTSL: cathepsin L, CTSO: cathepsin O, CTSS: cathespin S, CTSV: cathespin V, CTSZ: cathespin X/Z/P, FRET: Fluorescence Resonance Energy Transfer.
Supplier Page from R&D Systems, a Bio-Techne Brand for Cathepsin X/Z/P Protein
Available conjugates: Sizes Available: 10 ug