Folate and methylation status in relation to phosphorylated tau protein(181P) and beta-amyloid(1-42) in cerebrospinal fluid.
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 B(12) 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 beta-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, 41-60, and >60 years). CSF tHcy was predicted by concentrations of CSF cystathionine (beta = 0.478), folate (beta = -0.403), albumin (beta = 0.349), and age (beta = 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.
Obeid
Rima
R
Department of Clinical Chemistry and Laboratory Medicine and Neurology, Faculty of Medicine, University Hospital of Saarland, Homburg/Saar, Germany.
Kasoha
Mariz
M
Knapp
Jean-Pierre
JP
Kostopoulos
Panagiotis
P
Becker
George
G
Fassbender
Klaus
K
Herrmann
Wolfgang
W
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003545:Cysteine / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010766:Phosphorylation; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000134:cerebrospinal fluid; D014805:Vitamin B 12 / Q000097:blood / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D003545:Cysteine; D014805:Vitamin B 12