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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 A β  42 , 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.

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