Blood Kallikrein-8 and Non-Amnestic Mild Cognitive Impairment: An Exploratory Study

Sara Schramm; Nela Krizanovic; Ulla Roggenbuck; Karl-Heinz Jöckel; Arne Herring; Kathy Keyvani; Martha Jokisch

doi:10.3233/ADR-220073

Blood Kallikrein-8 and Non-Amnestic Mild Cognitive Impairment: An Exploratory Study

J Alzheimers Dis Rep. 2023 May 3;7(1):327-337. doi: 10.3233/ADR-220073. eCollection 2023.

Authors

Sara Schramm¹, Nela Krizanovic¹, Ulla Roggenbuck¹, Karl-Heinz Jöckel¹, Arne Herring², Kathy Keyvani², Martha Jokisch³

Affiliations

¹ Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² Institute of Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
³ Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

Background: Blood kallikrein-8 is supposed to be a biomarker for mild cognitive impairment (MCI) due to Alzheimer's disease (AD), a precursor of AD dementia. Little is known about the association of kallikrein-8 and non-AD type dementias.

Objective: To investigate whether blood kallikrein-8 is elevated in individuals with non-amnestic MCI (naMCI), which has a higher probability to progress to a non-AD type dementia, compared with cognitively unimpaired (CU) controls.

Methods: We measured blood kallikrein-8 at ten-year follow-up (T2) in 75 cases and 75 controls matched for age and sex who were participants of the population-based Heinz Nixdorf Recall study (baseline: 2000-2003). Cognitive performance was assessed in a standardized manner at five (T1) and ten-year follow-up. Cases were CU or had subjective cognitive decline (SCD) at T1 and had naMCI at T2. Controls were CU at both follow-ups. The association between kallikrein-8 (per 500 pg/ml increase) and naMCI was estimated using conditional logistic regression: odds ratios (OR) and 95% confidence intervals (95% CI) were determined, adjusted for inter-assay variability and freezing duration.

Results: Valid kallikrein-8 values were measured in 121 participants (45% cases, 54.5% women, 70.5±7.1 years). In cases, the mean kallikrein-8 was higher than in controls (922±797 pg/ml versus 884±782 pg/ml). Kallikrein-8 was not associated with having naMCI compared to being CU (adjusted; OR: 1.03 [95% CI: 0.80-1.32]).

Conclusion: This is the first population-based study that shows that blood kallikrein-8 tends not to be elevated in individuals with naMCI compared with CU. This adds to the evidence of the possible AD specificity of kallikrein-8.

Keywords: Alzheimer’s disease; Heinz Nixdorf Recall study; biomarker; dementia; kallikrein-8; mild cognitive impairment; neurodegeneration; neuropsin.