Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease

Area of Science:

• Neuroscience
• Biochemistry
• Radiology

Background:

• Brain metal homeostasis is critical for neurological health.
• Deregulation of metal balance can lead to oxidative stress in brain tissue.

Purpose of the Study:

• To investigate associations between cerebrospinal fluid (CSF) metal levels and markers of small vessel disease, specifically cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS).
• To explore relationships between CSF metal concentrations and CSF biomarkers for dementia, including amyloid-beta (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau).

Main Methods:

• A cross-sectional study involving 196 patients from a memory clinic investigation.
• Brain MRI was performed, and CSF was collected for analysis of metals, Aβ42, T-tau, P-tau, and CSF/serum albumin ratio.
• Generalized linear models were used for statistical analysis.

Main Results:

• No significant differences in CSF metal levels were observed across diagnostic groups.
• Elevated CSF iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratio (p < 0.05).
• CSF zinc correlated with higher CSF/serum albumin ratios. No direct association was found between CMBs or cSS and CSF iron, except in APOEɛ4 carriers where increased CSF iron was noted with more CMBs.

Conclusions:

• CSF iron levels are elevated in APOEɛ4 carriers with cerebral microbleeds, but not generally with other hemorrhagic markers of small vessel disease.
• The observed correlation between elevated CSF iron and copper with tau biomarkers may indicate increased neurodegeneration in affected patients.