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


CONCLUSIONS
Our results suggest an impairment of mitochondrial oxidative metabolism in brain cells of patients with Alzheimer's disease.
Laboratoire de Pathologie Cellulaire et Moléculaire en Nutrition, EP616 CNRS, Faculté de Médecine, Université de Nancy I, France.
N
N
Redjems-Bennani
C
C
Jeandel
E
E
Lefebvre
H
H
Blain
M
M
Vidailhet
J L
JL
Guéant
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000502:physiology; D002952:Citric Acid Cycle / Q000502:physiology; D005260:Female; D005650:Fumarates / Q000134:cerebrospinal fluid; D005973:Glutamine / Q000134:cerebrospinal fluid; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D012016:Reference Values; D013379:Substrate Specificity; D019802:Succinic Acid / Q000134:cerebrospinal fluid
D005650:Fumarates; D005973:Glutamine; D019344:Lactic Acid; C032005:fumaric acid; D019802:Succinic Acid