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.