Document Detail

Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment.
MedLine Citation:
PMID:  20491609     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Abnormalities in neurotrophic systems have been reported in Alzheimer's disease (AD), as shown by decreased serum brain-derived neurotrophic factor (BDNF) levels and association with BDNF genetic polymorphisms. In this study, we investigate whether these findings can be detected in patients with mild cognitive impairment (MCI), which is recognized as a high risk condition for AD. We also address the impact of these variables on the progression of cognitive deficits within the MCI-AD continuum.
METHODS: One hundred and sixty older adults with varying degrees of cognitive impairment (30 patients with AD, 71 with MCI, and 59 healthy controls) were longitudinally assessed for up to 60 months. Baseline serum BDNF levels were determined by sandwich ELISA, and the presence of polymorphisms of BDNF and apolipoprotein E (Val66Met and APOE*E4, respectively) was determined by allelic discrimination analysis on real time PCR. Modifications of cognitive state were ascertained for non-demented subjects.
RESULTS: Mean serum BDNF levels were reduced in patients with MCI and AD, as compared to controls (509.2+/-210.5; 581.9+/-379.4; and 777.5+/-467.8 pg/l respectively; P<0.001). Baseline serum BDNF levels were not associated with the progression of cognitive impairment upon follow-up in patients with MCI (progressive MCI, 750.8+/-463.0; stable MCI, 724.0+/-343.4; P=0.8), nor with the conversion to AD. Although Val66Met polymorphisms were not associated with the cross-sectional diagnoses of MCI or AD, the presence of Met-BDNF allele was associated with a higher risk of disease-progression in patients with MCI (OR=3.0 CI(95%) [1.2-7.8], P=0.02). We also found a significant interaction between the APOE*E4 and Met-BDNF allele increasing the risk of progression of cognitive impairment in MCI patients (OR=4.4 CI(95%) [1.6-12.1], P=0.004).
CONCLUSION: Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.
Orestes Vicente Forlenza; Breno Satler Diniz; Antonio Lucio Teixeira; Elida Benquique Ojopi; Leda Leme Talib; Vanessa Amaral Mendonça; Giselle Izzo; Wagner Farid Gattaz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry     Volume:  11     ISSN:  1814-1412     ISO Abbreviation:  World J. Biol. Psychiatry     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101120023     Medline TA:  World J Biol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  774-80     Citation Subset:  IM    
Laboratory of Neuroscience-LIM 27, Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, SP, Brazil.
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MeSH Terms
Analysis of Variance
Apolipoproteins E / blood,  genetics
Brain-Derived Neurotrophic Factor / blood*,  genetics*
Cognition Disorders / blood*,  genetics*
Cohort Studies
Disease Progression
Enzyme-Linked Immunosorbent Assay / methods
Follow-Up Studies
Longitudinal Studies
Polymorphism, Genetic / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Severity of Illness Index
Reg. No./Substance:
0/Apolipoproteins E; 0/Brain-Derived Neurotrophic Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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