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Association Study of the Decreased Serum BDNF Concentrations in Amnestic Mild Cognitive Impairment and the Val66Met Polymorphism in Chinese Han

J Clin Psychiatry 2008;69(7):1104-1111

Objective: Experimental and clinical data suggested that brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by declined cognitive function and has a high probability of evolving into AD. The aim of this study was to investigate serum BDNF concentrations in aMCI patients and determine whether there is an association of the BDNF gene Val66Met polymorphism with aMCI, cognitive function, and serum BDNF.

Method: Between April 2005 and January 2006, the present study recruited 99 aMCI patients who met diagnostic criteria for MCI proposed by the Mayo Clinic Alzheimer's Disease Research Center and 99 matched healthy controls from a population-based sample. All subjects underwent extensive assessment of cognitive function, measurement of serum BDNF by an enzyme-linked immunosorbent assay, and genotyping of the BDNF gene Val66Met polymorphism.

Results: The serum concentrations of BDNF in aMCI patients (median [interquartile range] =4.37 [2.35-6.40] ng/mL) were significantly lower than those of healthy controls (4.98 [3.50-7.33] ng/mL) (z = -2.449, p = .014). There were significant positive correlations between serum BDNF and scores on delayed recall in the Auditory Verbal Learning Test, which reflects episodic memory (r = 0.264, p = .008). No significant differences were found for either the genotype or allele distribution of BDNF Val66Met polymorphism between aMCI patients and control subjects. The BDNF Val66Met polymorphism was not associated with serum BDNF or cognitive function in aMCI patients.

Conclusions: This study suggests that reduced BDNF levels may play a role in the pathophysiology of aMCI, and the BDNF gene Val66Met polymorphism may not be an important factor in susceptibility to aMCI.