Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment.
BACKGROUND
Alzheimer's disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD.


OBJECTIVE
To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B(12) and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group.


METHODS
The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B(12) in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression.


RESULTS
We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B(12) levels and MTHFR status.


CONCLUSIONS
We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.
Religa
D
D
Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. Dorota.Religa@neurotec.ki.se
Styczynska
M
M
Peplonska
B
B
Gabryelewicz
T
T
Pfeffer
A
A
Chodakowska
M
M
Luczywek
E
E
Wasiak
B
B
Stepien
K
K
Golebiowski
M
M
Winblad
B
B
Barcikowska
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D003072:Cognition Disorders / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D014805:Vitamin B 12 / Q000097:blood*
D001057:Apolipoproteins E; D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12