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General Clinical Chemistry |
Departments of1 Clinical Chemistry and Laboratory Medicine and 2 Neurology, Faculty of Medicine, University Hospital of Saarland, Homburg/Saar, Germany.
aAddress correspondence to this author at: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Kirrberger Straße, Gebäude 57, 66421 Homburg, Germany. Fax 49-6841-1630703; 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 ß-amyloid(142) 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, 4160, and >60 years). CSF tHcy was predicted by concentrations of CSF cystathionine (ß = 0.478), folate (ß = 0.403), albumin (ß = 0.349), and age (ß = 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.
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