Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer's disease and associated with CSF-TAU and FDG-PET

Oliver Goldhardt; Inanna Warnhoff; Igor Yakushev; Ilijana Begcevic; Hans Förstl; Viktor Magdolen; Antoninus Soosaipillai; Eleftherios Diamandis; Panagiotis Alexopoulos; Timo Grimmer

doi:10.1186/s40035-019-0168-6

Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer's disease and associated with CSF-TAU and FDG-PET

Transl Neurodegener. 2019 Aug 27:8:25. doi: 10.1186/s40035-019-0168-6. eCollection 2019.

Authors

Affiliations

¹ 1Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675 Munich, Germany.
² 2Department of Nuclear Medicine, TUM-NIC, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675 Munich, Germany.
³ 5Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, Ontario M5S 1A8 Canada.
⁴ 3Department of Obstetrics & Gynecology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675 Munich, Germany.
⁵ 4Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray St., Toronto, Ontario M5T 3L9 Canada.
⁶ 6Department of Psychiatry, University hospital of Rion, University of Patras, 26500 Rion Patras, Patras, Greece.

Abstract

Background: Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer's disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.

Methods: KLK levels in cerebrospinal fluid (CSF), as determined by ELISA, were compared between 32 AD patients stratified to A/T/(N) system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers. Associations between KLK levels and clinical severity, CSF and positron emission tomography (PET) based AD biomarkers were tested for.

Results: Levels of KLK6 and KLK10 were significantly increased in AD. KLK6 differed significantly between AD A+/T+/N+ and AD A+/T-/N+ or NC with an AUC of 0.922. CSF pTau and tTau levels were significantly associated with KLK6 in AD.

Conclusions: KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.

Keywords: Alzheimer’s disease (AD); Amyloid 1–42; Aβ1–42; Aβ42; Cerebral amyloid load; Cerebrospinal fluid (CSF); KLK10; KLK6; KLK8; Kallikrein-like peptidase (KLK); Phospho tau; Positron emission tomography (PET); Tau protein; Total tau; pTau; tTau.