Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients

Gerontology. 1998;44(5):300-4. doi: 10.1159/000022031.


Background: Impaired oxidative and energy metabolism are important features in Alzheimer's disease. These metabolic abnormalities may induce functional disturbances and are associated with significant cognitive impairment.

Objective: To determine whether mitochondrial function is altered by Alzheimer's disease, a quantitative analysis of substrates that enter the tricarboxylic acid cycle was carried out in cerebrospinal fluid (CSF) from Alzheimer patients.

Methods: Organic acid levels related to carbohydrate oxidation were measured in CSF from patients affected by dementia of Alzheimer type (n = 17) and from nondemented elderly controls (n = 17) using a gas chromatography/mass spectrometry system. CSF glucose and glutamine concentrations were determined by a quantitative enzymatic method and by ion exchange chromatography, respectively.

Results: Compared to age-matched controls, patients had a higher CSF level of lactate (p = 0.002) and a lower mean level of succinate (p = 0.002), fumarate (p = 0.003) and glutamine (p = 0.0005). The CSF glucose level was not modified.

Conclusion: Our results suggest an impairment of mitochondrial oxidative metabolism in brain cells of patients with Alzheimer's disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Cerebrospinal Fluid / physiology
  • Citric Acid Cycle / physiology
  • Female
  • Fumarates / cerebrospinal fluid
  • Glutamine / cerebrospinal fluid
  • Humans
  • Lactic Acid / cerebrospinal fluid
  • Male
  • Mitochondria / physiology*
  • Reference Values
  • Substrate Specificity
  • Succinic Acid / cerebrospinal fluid


  • Fumarates
  • Glutamine
  • Lactic Acid
  • fumaric acid
  • Succinic Acid