AUTHOR=Lu Yuanyuan 

TITLE=Early increase of cerebrospinal fluid 14-3-3ζ protein in the alzheimer's disease continuum

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.941927

DOI=10.3389/fnagi.2022.941927

ISSN=1663-4365

ABSTRACT=Background: Previous research has shown that 14-3-3ζ is increased in neurofibrillary tangles (NFTs) of human Alzheimer's Disease (AD) brains and stimulates tau phosphorylation. Cerebrospinal fluid (CSF) 14-3-3ζ along the AD continuum remains to be explored.
Methods: We analyzed 113 cognitive normal (CN) controls, 372 patients with cognitive impairment (MCI), and 225 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative database. CSF 14-3-3ζ protein was measured by Mass Spectrometry.
Results: We observed higher CSF 14-3-3ζ in the MCI group versus the CN group and in the AD group versus the MCI or CN group. 14-3-3ζ was able to distinguish AD from CN and MCI. High 14-3-3ζ predicted conversion from MCI to AD. In CSF, phosphorylated tau at threonine 181 and total-tau were associated with 14-3-3ζ in MCI and AD groups, and beta-amyloid (Aβ) 42 correlated with 14-3-3ζ in the MCI group. Baseline high 14-3-3ζ was associated with cognitive decline, brain atrophy, glucose hypometabolism, and Aβ deposition in MCI and AD at baseline and follow-up.
Conclusion: Our findings revealed the potential diagnostic and prognostic utility of CSF 14-3-3ζ in the AD continuum. 14-3-3ζ could be a promising therapeutic target for the intervention of AD.