Received on January 2, 2007
Accepted on February 13, 2007

General Clinical Chemistry

Folate and Methylation Status in Relation to Phosphorylated Tau Protein_(181P) and -Amyloid(1-42) in Cerebrospinal Fluid

¹ Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, Homburg/Saar, Germany
² Department of Neurology, Faculty of Medicine, University Hospital of Saarland, Homburg/Saar, Germany

^* To whom correspondence should be addressed. E-mail: kchwher{at}uniklinikum-saarland.de.

Background:Increased plasma total homocysteine (tHcy) is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained.

Methods: We evaluated concentrations of tHcy, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), folate, and vitamin B₁₂ in cerebrospinal fluid (CSF) and plasma or serum from 182 patients with different neurological disorders. We measured concentrations of phosphorylated tau protein (P-tau; 181P) and -amyloid(1-42) in the CSF.

Results: Aging was associated with higher concentrations of tHcy and SAH in the CSF, in addition to lower concentrations of CSF folate and lower SAM:SAH ratio. Concentrations of CSF SAH and CSF folate correlated significantly with those of P-tau (r = 0.46 and r = -0.28, respectively). Moreover, P-tau correlated negatively with SAM:SAH ratio (r = -0.40, P <0.001). The association between SAH and higher P-tau was observed in 3 age groups (<41, 41 to 60, and >60 years). CSF tHcy was predicted by concentrations of CSF cystathionine ( = 0.478), folate ( = -0.403), albumin ( = 0.349), and age ( = 0.298).

Conclusions: tHcy concentration in the brain is related to age, B vitamins, and CSF albumin. Increase of CSF SAH is related to increased CSF P-tau; decreased degradation of P-tau might be a plausible explanation. Disturbed methyl group metabolism may be the link between hyperhomocysteinemia and neurodegeneration. Lowering tHcy and SAH might protect the brain by preventing P-tau accumulation.