Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) is an activity-dependent secreted protein that is critical to organization of neuronal networks and synaptic plasticity, especially in the hippocampus. We tested hypothesis that reduced CSF BDNF is associated with age-related cognitive decline.
CSF concentration of BDNF, Abeta(42) and total tau were measured in 128 cognitively normal adults (Normals), 21 patients with Alzheimer's disease (AD), and nine patients with Mild Cognitive Impairment. Apolipoprotein E and BDNF SNP rs6265 genotype were determined. Neuropsychological tests were performed at baseline for all subjects and at follow-up visits in 50 Normals. CSF BDNF level was lower in AD patients compared to age-matched Normals (p = 0.02). CSF BDNF concentration decreased with age among Normals and was higher in women than men (both p<0.001). After adjusting for age, gender, education, CSF Abeta(42) and total tau, and APOE and BDNF genotypes, lower CSF BDNF concentration was associated poorer immediate and delayed recall at baseline (both p<0.05) and in follow up of approximately 3 years duration (both p<0.01).


CONCLUSIONS
Reduced CSF BDNF was associated with age-related cognitive decline, suggesting a potential mechanism that may contribute in part to cognitive decline in older individuals.
Li
Ge
G
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA. gli@u.washington.edu
Peskind
Elaine R
ER
Millard
Steven P
SP
Chi
Peter
P
Sokal
Izabela
I
Yu
Chang-En
CE
Bekris
Lynn M
LM
Raskind
Murray A
MA
Galasko
Douglas R
DR
Montine
Thomas J
TJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid* / Q000235:genetics; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000235:genetics / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D055815:Young Adult
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)