Imagine you’re at a bustling farmers market, trying to find the ripest peaches. You might pick up one peach and examine its color and texture. Then, you take it home and discover that its sweetness perfectly complements your morning yogurt. In a similar way, scientists have been studying the relationship between clusterin, a glycoprotein associated with Alzheimer’s disease (AD), and various biomarkers of AD pathology. This study delved into the impact of clusterin levels in cerebrospinal fluid (CSF) on cognitive function and markers of physiological changes in individuals diagnosed with mild cognitive impairment (MCI). Using a longitudinal cohort from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, the researchers found that CSF clusterin correlated with key biomarkers related to AD pathology, such as amyloid-beta-42 (Aβ42), total tau (T-tau), and brain volume. They also discovered that baseline CSF clusterin levels could predict cognitive shifts in MCI patients. Interestingly, alterations in certain brain regions mediated the effect of clusterin on cognition. These findings highlight clusterin’s potential as a protective factor for cognitive abilities in individuals experiencing early memory loss. To learn more about this groundbreaking research, check out the full article!

BackgroundClusterin, a glycoprotein implicated in Alzheimer’s disease (AD), remains unclear. The objective of this study was to analyze the effect of cerebrospinal fluid (CSF) clusterin in relation to AD biomarkers using a longitudinal cohort of non-demented individuals.MethodsWe gathered a sample comprising 86 individuals under cognition normal (CN) and 134 patients diagnosed with MCI via the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To investigate the correlation of CSF clusterin with cognitive function and markers of key physiological changes, we employed multiple linear regression and mixed-effect models. We undertook a causal mediation analysis to inspect the mediating influence of CSF clusterin on cognitive abilities.ResultsPathological characteristics associated with baseline Aβ42, Tau, brain volume, exhibited a correlation with initial CSF clusterin in the general population, Specifically, these correlations were especially prominent in the MCI population; CSF Aβ42 (PCN = 0.001; PMCI = 0.007), T-tau (PCN < 0.001; PMCI < 0.001), and Mid temporal (PCN = 0.033; PMCI = 0.005). Baseline CSF clusterin level was predictive of measurable cognitive shifts in the MCI population, as indicated by MMSE (β = 0.202, p = 0.029), MEM (β = 0.186, p = 0.036), RAVLT immediate recall (β = 0.182, p = 0.038), and EF scores (β = 0.221, p = 0.013). In MCI population, the alterations in brain regions (17.87% of the total effect) mediated the effect of clusterin on cognition. It was found that variables such as age, gender, and presence of APOE ε4 carrier status, influenced some of these connections.ConclusionOur investigation underscored a correlation between CSF clusterin concentrations and pivotal AD indicators, while also highlighting clusterin’s potential role as a protective factor for cognitive abilities in MCI patients.

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