Cathepsin B Gene Knockout Improves Memory Deficits in AD and Aging Models

Animal ModelhAPP IsotypeCTSB Knockout Improves Memory Deficits and Outcomes in hAPP AD ModelsReferences
Isotype, Cell Typeβ-Secretase Siteγ-Secretase SiteMemory DeficitsCellular and Biomarker FeaturesPathology
AgingMouse APP isoforms of 695 in neurons and isoforms 751 and 770 in gliaWTWT↓Memory deficits↓Activated macrophages, ↓inflammatory cytokines, ↓oxidative stress, ↑long-term potentiationndTerada et al., 2010; Ni et al., 2019
Periodontitis ADMouse APP isoforms of 695 in neurons and 751 and 770 in gliaWTWT↓Memory deficits↓Activated macrophages
↓Aβ (1-42), ↓inflammatory cytokines
ndWu et al., 2017
ADhAPP-WT-695, neuronal expression (PDGF promoter)WTWTn/a↓Aβ (1–42) by ∼70%
β (1–40) by ∼70%
↓CTFβ by 40%, ↑sAPPα by 60%, ↓WT β-secretase activity
n/aHook et al., 2009
ADhAPP-WT-Lon-695, neuronal expression (PDGF promoter)WTLon, V717I↓Memory deficits↓Aβ(1–40) by 85%
↓Aβ(1–42) by 87%
↓pGluAβ(3–40) by 65%
↓pGluAβ(3–42) by 92%
↓CTFβ by 60%
↑sAβPPα by 60%
↓WT β-secretase activity
↓Aβ plaque by 85%, ↓pGluAβ plaque by 46%Kindy et al., 2012; Hook et al., 2014b
ADhAPP-Swe-Lon-695, neuronal expression (PDGF promoter)Swe, K670N/M671LLon, V717INo effect on memory deficitsNo effects on Aβ(1–42), CTFβ, or APPαNo effect on amyloid plaqueKindy et al., 2012
ADhAPP-Swe-Ind-695, neuronal expression (PDGF promoter)Swe K670N/M671LInd, V717Fn/aNo effects on Aβ, CTFβ, or sAPPαn/aHook et al., 2009
ADhAPP-Swe-Ind-751/770, neuronal expression (PDGF promoter), J20 line, introns modified, PDAPP)SweIndndNo change in fIAPP, β-CTF, α-sAPP, or α-CTF
↑Aβ(1–42)/Aβ(1–x) ratio by ∼25%
Elevated plaque loadMueller-Steiner et al., 2006
ADhAPP-751/770, neuronal expression (PDGF promoter, I63 line, introns modified, PDAPP)WTWTndNo change in hippocampal Aβ42, ↑cortical Aβ42 by 12%ndWang et al., 2012
  • nd, not determined; n/a, not applicable.