Folate and methylation status in relation to phosphorylated tau protein(181P) and beta-amyloid(1-42) in cerebrospinal fluid

Clin Chem. 2007 Jun;53(6):1129-36. doi: 10.1373/clinchem.2006.085241. Epub 2007 Mar 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cysteine / blood
  • Cysteine / cerebrospinal fluid
  • Female
  • Folic Acid / blood*
  • Folic Acid / cerebrospinal fluid*
  • Humans
  • Male
  • Methylation
  • Middle Aged
  • Nervous System Diseases / blood
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / metabolism*
  • Neurodegenerative Diseases / blood
  • Neurodegenerative Diseases / cerebrospinal fluid
  • Neurodegenerative Diseases / metabolism
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / metabolism*
  • Phosphorylation
  • S-Adenosylhomocysteine / blood
  • S-Adenosylhomocysteine / cerebrospinal fluid
  • Vitamin B 12 / blood
  • Vitamin B 12 / cerebrospinal fluid
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Folic Acid
  • S-Adenosylhomocysteine
  • Cysteine
  • Vitamin B 12