Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.
Level 4 - case-series / case-control
Case-control post-mortem tissue and clinical biomarker study
PubMed 27276998 · doi:10.1038/srep27524
What was done
Mass spectrometry was used to quantify metabolites and metals across seven post-mortem brain regions from 9 patients with Alzheimer's disease (AD) and 9 controls. In addition, an ante-mortem case-control comparison evaluated plasma glucose and copper concentrations in patients with AD and controls.
What was found
Glucose, sorbitol, and fructose concentrations were elevated across all seven examined AD brain regions, whereas brain copper levels were significantly decreased across all regions compared to controls (all P < 0.0001). Conversely, ante-mortem plasma glucose and plasma copper levels showed no significant differences between AD patients and controls (numerical values for plasma and brain tissue were not provided in the abstract).
Why it matters
The findings indicate that cerebral glucose accumulation, activation of the polyol pathway, and brain copper deficiency occur locally across multiple brain regions in Alzheimer's disease without corresponding systemic changes in blood plasma.
Limits
The post-mortem cohort was very small (9 AD cases and 9 controls). The sample size, demographics, and clinical details for the ante-mortem plasma cohort were not reported in the abstract. As a cross-sectional post-mortem study, it cannot establish whether these metabolic abnormalities are a cause or an end-stage consequence of neurodegeneration.
Cited by
- supports A June 2016 study in Scientific Reports examining 18 postmortem brains (9 with and 9 without Alzheimer's) found that fructose and sorbitol were increased four- to six-fold in Alzheimer's brains compared to controls.