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Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer's Disease: A Pilot Study

Thordardottir, S; Almkvist, O; Johansson, C; Zetterberg, H; Blennow, K; Graff, C; (2020) Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer's Disease: A Pilot Study. Journal of Alzheimer's Disease 10.3233/JAD-191261. (In press). Green open access

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Abstract

BACKGROUND: YKL-40 and neurogranin are promising additional cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) which reflect different underlying disease mechanisms. OBJECTIVE: To compare the levels of CSF YKL-40 and neurogranin between asymptomatic carriers of familial AD (FAD) mutations (MC) and non-carriers (NC) from the same families. Another objective was to assess changes in YKL-40 and neurogranin, from the presymptomatic to clinical phase of FAD. METHODS: YKL-40 and neurogranin, as well as Aβ42, total tau-protein, and phospho-tau, were measured in the CSF of 14 individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G), and PSEN1 (p.H163Y), as well as in 17 NC from the same families. Five of the MC developed mild cognitive impairment (MCI) during follow-up. RESULTS: In this pilot study, there was no difference in either CSF YKL-40 or neurogranin when comparing the presymptomatic MC to the NC. YKL-40 correlated positively with expected years to symptom onset and to age in both the MC and the NC, while neurogranin had no correlation to either variable in either of the groups. A subgroup of the participants underwent more than one CSF sampling in which half of the MC developed MCI during follow-up. The longitudinal data showed an increase in YKL-40 levels in the MC as the expected symptom onset approached. Neurogranin remained stable over time in both the MC and the NC. CONCLUSION: These findings support a positive correlation between progression from presymptomatic to symptomatic AD and levels of CSF YKL-40, but not neurogranin.

Type: Article
Title: Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer's Disease: A Pilot Study
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-191261
Publisher version: http://dx.doi.org/10.3233/JAD-191261
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, chitinases, genetics, mutation, neurogranin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10103834
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