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Widespread Decreases in Cerebral Copper Are Common to Parkinson's Disease Dementia and Alzheimer's Disease Dementia

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This post-mortem study measured eight essential metals and selenium in nine brain regions from people who died with Parkinson’s disease dementia and from age-matched controls. Copper was the most consistently altered metal: it was lower in seven of the nine regions in dementia cases. The authors report that four of these regions showed similar decreases in their earlier work on Alzheimer’s disease dementia, so the finding points to copper depletion rather than copper excess.

Key numbers

All values are means (95% confidence interval) in µmol/kg dry weight; dementia cases n = 9.

  • Substantia nigra copper: 201.8 (174.1 to 229.6) in cases versus 306.8 (248.4 to 365.2) in 9 controls (p = 0.003) (Table 4A, p. 5).
  • Cingulate gyrus: 181.6 versus 249.0 in 27 controls (p = 0.009) (Table 4B, p. 5).
  • Hippocampus: 177.4 versus 303.1 in 27 controls (p = 0.0010) (Table 4D, p. 6).
  • Primary motor cortex: 219.1 versus 403.5 in 26 controls (p = 0.0010) (Table 4I, p. 7).
  • Cerebellum: 324.2 versus 328.3 in 9 controls (p = 0.6, not significant) (Table 4H, p. 7).
  • The authors give control-region copper as averaging about 300 µmol/kg, or 18.9 µg/g dry weight (Results, p. 4).

Methods (brief)

Brain regions from the Multiple Sclerosis and Parkinson’s Tissue Bank at Imperial College London were dissected with a ceramic scalpel, dried to constant weight, digested and analyzed by ICP-MS with three replicate runs. Case-control differences were tested by Mann-Whitney U-test, with power calculations for small groups.

Evidence fitness

Supports human brain copper reference values and the observation that copper is depleted, not raised, in several brain regions in Parkinson’s and Alzheimer’s dementia. It does not measure dietary exposure and does not support claims that dietary copper causes dementia.

Limitations

Very small groups, post-mortem tissue with delays of up to 48 hours, and controls pooled from several earlier cohorts for some regions. Dementia cases were about 10 years younger than controls.

Update history

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