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Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer’s disease

¹ Department of Geriatric Medicine, Hôpital Sud, Amiens, France
² Laboratory of Biochemistry, Hôpital de Brabois, Vandoeuvre lès Nancy, France
³ Baylor, University Medical Center, Institute of Metabolic Disease, Dallas, Texas, USA
⁴ Laboratory of Biochemistry, Hôpital Central, Nancy, France
⁵ Laboratory of Immunology, Faculty of Medicine, Vandoeuvre lès Nancy, France
⁶ Laboratory of Biochemistry, INSERM U724, Faculty of Medicine, Vandoeuvre lès Nancy, France

Correspondence to:
Correspondence to:
Dr J M Serot
Centre Saint Vincent, Hôpital Sud, Amiens 80054, France; serot.jean-marie{at}chu-amiens.fr

ABSTRACT
Background: Homocysteine may be involved in the pathogenesis of late onset Alzheimer’s disease. It is implicated in the metabolism of several important pathways in the brain. Methylmalonic acid (MMA) is related to the metabolism of branched chained amino acids and fatty acids.

Objectives: To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer’s disease, and younger healthy controls.

Subjects: CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60.

Results: CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)) There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml).

Conclusions: CSF total homocysteine is not increased in Alzheimer’s disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.

Abbreviations: MMA, methylmalonic acid; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders–Alzheimer’s Disease and Related Disorders Association

Keywords: cerebrospinal fluid; homocysteine; methylmalonic acid; Alzheimer’s disease

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