Copper, Ceruloplasmin, Zinc, and Manganese Levels in Brain and Biological Fluids from Parkinson’s Disease Patients: Systematic Review and Meta-Analysis

TL;DR

This study reviews and analyzes metal levels in Parkinson’s disease patients, finding changes in copper, zinc, and manganese that may be linked to the disease.

Contribution

The study provides a comprehensive meta-analysis of metal levels in PD patients across multiple biological samples.

Findings

PD patients had decreased copper in the substantia nigra and other brain areas.

Zinc levels were decreased in serum/plasma but increased in whole blood and hair.

Hair manganese levels were increased in PD patients compared to controls.

Abstract

The present systematic review and meta-analysis aims to establish whether the brain, cerebrospinal fluid (CSF), serum/plasma whole blood, urine, and hair levels of copper, ceruloplasmin, zinc, and manganese are related to the risk for Parkinson’s disease (PD). We reviewed the PubMed and Web of Science Core Collection databases from 1966 to 29 November 2025, and identified references of interest for this topic. We performed the meta-analysis of eligible studies that followed the PRISMA and MOOSE guidelines, with the R software package meta R 4.2.0 version. When compared to age- and sex-matched controls, PD patients showed decreased concentrations of copper in the substantia nigra and other brain areas, a trend towards increased CSF and decreased serum/plasma copper levels, decreased serum/plasma ceruloplasmin levels, decreased zinc levels in serum/plasma and increased zinc in whole blood and hair, and increased hair manganese levels. These results suggest an association between these transition metals and risk for PD.

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