Kallikrein‐8 inhibition attenuates Alzheimer's disease pathology in mice. Issue 12 (18th June 2016)

• Record Type: Journal Article
• Authors: Herring, Arne; Münster, Yvonne; Akkaya, Tamer; Moghaddam, Sahar; Deinsberger, Katharina; Meyer, Jakob; Zahel, Julia; Sanchez‐Mendoza, Eduardo; Wang, Yachao; Hermann, Dirk M.; Arzberger, Thomas; Teuber‐Hanselmann, Sarah; Keyvani, Kathy
• Is Part Of: Alzheimer's & dementia. Volume 12:Issue 12(2016)
• Page Start: 1273
• Page End: 1287
• Publication Date: 2016-06-18
• Subjects: Alzheimer's disease -- Kallikrein‐8 -- Intraventricular antibody delivery -- Ephrin receptor B2 -- Anxiety -- Neuroplasticity -- Aβ pathology -- Aβ clearance -- Autophagy -- tau pathology; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2016.05.006
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: Memory loss and increased anxiety are clinical hallmarks of Alzheimer's disease (AD). Kallikrein‐8 is a protease implicated in memory acquisition and anxiety, and its mRNA is known to be up‐regulated in AD‐affected human hippocampus. Therefore, an involvement of Kallikrein‐8 in Alzheimer's pathogenesis is conceivable but remains to be proved. Methods: We determined the cerebral expression of Kallikrein‐8 mRNA and protein during the course of AD in patients and in transgenic mice and tested the impact of Kallikrein‐8 inhibition on AD‐related pathology in mice and in primary glial cells. Results: Kallikrein‐8 mRNA and protein were up‐regulated in both species at incipient stages of AD. Kallikrein‐8 inhibition impeded amyloidogenic amyloid‐precursor‐protein processing, facilitated amyloid β (Aβ) clearance across the blood‐brain‐barrier, boosted autophagy, reduced Aβ load and tau pathology, enhanced neuroplasticity, reversed molecular signatures of anxiety, and ultimately improved memory and reduced fear. Discussion: Kallikrein‐8 is a promising new therapeutic target against AD.