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

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.

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.

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.

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.

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