Association between default mode network functional connectivity and plasma p-Tau217 levels in patients with mild cognitive impairment
Shang Zhang, Haoyu Li, Junyao Wang, Duan Liu, Hongyu Zhang, Liang Gong
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Longitudinal |
|---|---|
| Sample size | 64 |
| Population | 32 patients with mild cognitive impairment and 32 healthy controls |
| Topics | Default mode network |
| Key findings | MCI patients showed higher plasma p-Tau217 and altered default mode network connectivity compared with controls. Within the MCI group, higher p-Tau217 correlated with weaker left precuneus–dorsolateral prefrontal connectivity and with worse global cognition, executive function, and visuospatial performance. The authors suggest this points to a potential link between peripheral tau pathology and network dysfunction. |
Abstract
Background: Mild cognitive impairment (MCI) is a critical stage in the Alzheimer's disease continuum, yet accessible biomarkers reflecting both peripheral pathology and central network dysfunction are insufficient. This study investigated whether default mode network (DMN) functional connectivity correlates with plasma phosphorylated tau 217 (p-Tau217) in MCI patients.Methods: Thirty‑two MCI patients and 32 healthy controls underwent neuropsychological assessment, plasma p‑Tau217 measurement, and resting‑state fMRI. Seed‑based functional connectivity was analyzed using five DMN regions (medial prefrontal, bilateral posterior cingulate, bilateral precuneus). Group comparisons and partial Spearman correlations were performed with age, sex, and education as covariates. Support vector machine classification was exploratory.Results: MCI patients showed lower cognition and higher p‑Tau217 than controls. They exhibited increased DMN connectivity with dorsolateral prefrontal and inferior parietal regions, and decreased connectivity within posterior and medial DMN. In MCI, p‑Tau217 negatively correlated with left precuneus‑left dorsolateral prefrontal connectivity (rs = −0.38, p = 0.034) and left precuneus‑right dorsolateral prefrontal connectivity (rs = −0.37, p = 0.036). Higher p‑Tau217 also correlated with worse global cognition, executive function, and visuospatial performance. A combined model using DMN features and p‑Tau217 achieved better classification than either alone.Conclusions: MCI patients have elevated p‑Tau217 and altered DMN connectivity. The association between p‑Tau217 and precuneus‑prefrontal connectivity suggests a potential link between peripheral tau pathology and network dysfunction. Combined blood and neuroimaging biomarkers warrant further validation in larger longitudinal cohorts with confirmed AD pathology.
Comparable studies
Other observational and cohort studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A default mode of brain function Normal adult human brain | 2001 | Observational study | |
| Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects | 2008 | Observational cohort | |
| Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls | 2005 | Observational cohort | n = 20 |
| Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls | 2011 | Observational cohort | |
| The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects | 2008 | Observational study |