Cerebrospinal Fluid Protein Sheds Light on Alzheimer’s Disease Progression

Published on July 29, 2022

Imagine you’re in a maze, trying to find your way out. As you explore, you come across glowing footprints on the ground. These footprints represent a protein called 14-3-3ζ, which has been found to increase in the cerebrospinal fluid (CSF) of people with Alzheimer’s disease (AD). In a recent study, researchers analyzed CSF samples from individuals at different stages of the AD continuum – cognitive normal controls, patients with mild cognitive impairment (MCI), and patients with AD dementia. They discovered that CSF 14-3-3ζ levels were elevated in both the MCI group compared to the control group, as well as the AD group compared to both the MCI and control groups. This suggests that CSF 14-3-3ζ could serve as a distinguishing marker for AD and potentially predict conversion from MCI to AD. In addition, higher levels of CSF 14-3-3ζ were associated with cognitive decline, brain atrophy, glucose hypometabolism, and amyloid-beta (Aβ) deposition. These findings highlight the potential diagnostic and prognostic role of CSF 14-3-3ζ in AD and suggest it as a possible target for therapeutic interventions. To learn more about this fascinating research, check out the full article!

BackgroundThe earlier research has shown that the 14-3-3ζ is increased in neurofibrillary tangles (NFTs) of human Alzheimer’s disease (AD) brains and stimulates the tau phosphorylation. Cerebrospinal fluid (CSF) 14-3-3ζ along the AD continuum remains to be explored.MethodsWe analyzed 113 cognitive normal (CN) controls, 372 patients with mild 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.ResultsWe observed higher CSF 14-3-3ζ in the MCI group vs. the CN group and in the AD group vs. the MCI or CN group. The 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.ConclusionOur findings revealed the potential diagnostic and prognostic utility of CSF 14-3-3ζ in the AD continuum. The 14-3-3ζ could be a promising therapeutic target for the intervention of AD.

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