CSF/serum folate gradient: physiology and determinants with special reference to dementia.
BACKGROUND
Folate depletion has been implicated as a risk factor for neurodegenerative disorders. We hypothesized that transport of folate to the cerebrospinal fluid (CSF) compartment could be involved in the pathophysiology of these disorders.


METHODS
The CSF/serum folate gradient (R(CSF/S)) was studied in 205 subjects with suspected cognitive disorder. Its relation to clinical and biochemical indices, including the integrity of the blood-CSF barrier, were characterized.


RESULTS
In subjects who were diagnosed as nondemented (ND) the mean R(CSF/S )+/- SD was 2.46 +/- 0.62 versus 2.09 +/- 0.67 (p = 0.008) in the dementia subgroup with a vascular component (VaD + mixed). The ND subgroup had higher CSF folate (p = 0.001) and lower serum homocysteine values (p = 0.001) than the VaD + mixed subgroup. The folate gradient R(CSF/S) was negatively correlated with serum folate (p < 0.001, R(2) = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (beta = -0.235). The Alzheimer patients had R(CSF/S) and albumin ratios similar to the ND subjects.


CONCLUSIONS
The R(CSF/S) was significantly lower in the VaD + mixed dementia subgroup, suggestive of a defect in the transport of folate over the choroid plexus that seems to be characteristic of, and limited to, the VaD + mixed dementia subgroup.
Hagnelius
Nils-Olof
NO
Department of Geriatrics, Orebro University Hospital, Orebro, Sweden. nils-olof.hagnelius@orebroll.se
Wahlund
Lars-Olof
LO
Nilsson
Torbjörn K
TK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000453:epidemiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D016022:Case-Control Studies; D002831:Choroid Plexus / Q000378:metabolism; D015140:Dementia, Vascular / Q000097:blood / Q000134:cerebrospinal fluid / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000134:cerebrospinal fluid*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood
D012709:Serum Albumin; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12