Folate and Homocysteine in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease or Dementia: A Case Control Study

Abstract

Background: Amyloid deposition in the brain is an early event in Alzheimer’s disease (AD), but a dysfunction of the blood-brain barrier or a disturbance in the metabolism of folate and homocysteine (Hcy) may affect the development of dementia. We investigated if the concentrations of folate and Hcy would be modified in cerebrospinal fluid (CSF) of clinically diagnosed AD patients. Methods: We included 70 AD patients, 33 patients with another type of dementia (nAD) and 30 age-matched control subjects. Plasma Hcy was assayed as well as Hcy, folate, Aβ1-42 and T-tau in CSF. We used ANOVAs for comparison between groups, and then pairwise comparisons by Wilcoxon tests with Bonferroni-corrected p values. Correlations were tested with the Spearman’s rank test. Results: Levels of Aβ1-42, T-tau and folates in CSF were significantly different between groups, but not Hcy. In addition, the average folate in CSF was lower in AD patients compared with controls (18.7 ± 2.4 vs. 20.3 ± 1.7 nmol/l, Bonferroni-corrected p value < 0.02). There was no correlation between Aβ1-42 or T-tau and folate or Hcy in CSF, regardless of the group. In the AD group, there was a significant inverse correlation between Hcy and folate in CSF (ρ = –0.63, p < 0.0001), whereas in the nAD group, a significant correlation was found for Hcy between plasma and CSF (ρ = 0.59, p < 0.0005). Conclusion: The concentration of folate in CSF was found to be decreased in AD patients. These findings support the hypothesis of a possible role of folate in the onset or worsening of AD.

Alterations in metabolic pathways and networks in Alzheimer’s disease

“…We were unable to replicate some prior findings because of low levels of some metabolites in lumbar CSF compared with ventricular CSF (for example, NE). Yet, our findings complement prior findings in pointing to changes within key pathways; for example, studies have reported changes in cysteine levels in AD, 32, 33 which seem related to our observation of alteration in MET and the GSH/MET ratio, although we could not measure cysteine. The same applies for observations with the VMA end product, NE.…”

Nutrients required for phospholipid synthesis are lower in blood and cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease dementia

“…Previous studies also reported lower serum folate concentration in MCI [31,32], although this has not been consistently found [33,34]. Similarly, some studies found no differences in CSF folate in AD compared with control subjects [35,36], whereas other found lower CSF folate in AD than in control subjects [37][38][39]. In addition, according to a meta-analysis, AD patients generally show lower serum folate levels compared with control subjects [11].…”

Optimizing Diagnosis and Management in mild-to-moderate Alzheimer’s Disease

“…Results from the Memory and Aging Project indicated the concentrations of docosahexanoic acid in phosphatidylserine of mid-frontal and superior temporal cortices were lower in patients with AD versus those without any cognitive impairment [7]. It has also been shown folate levels in the cerebrospinal fluid (CSF) of patients with AD are significantly lower than those of age-matched normal controls [8]. …”