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P3‐034: Detection of gender specific differences in the diagnosis of Alzheimer's disease via high‐resolution blood‐gene expression
Author(s) -
Einstein Richard,
FehlbaumBeurdeley Pascale,
JarrigeLe Prado AnneCharlotte,
Zhou Weiyin,
Sol Olivier,
Jordan Heather,
Lei Lin,
Wu Darong
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.1211
Subject(s) - disease , dementia , population , medicine , alzheimer's disease , gene , computational biology , bioinformatics , biology , genetics , environmental health
BDNF, total tau and Ab42 were measured using an X-MAP-based assay. APOE and BDNF SNP rs6265 genotypes were determined. 50 older normals had at least one follow-up visit (mean 6 SD 4.0 6 1.1, Range1⁄4 2 6) with an average length of follow-up of 3.3 years. Neuropsychological tests included: Paragraph Recall, Category Fluency, and Trail Making, Parts A and B. Results: CSF BDNF was lower in AD compared to older normals (p 1⁄4 0.02). Frequencies of Met-BDNF genotype were not different among older normals, MCI, and AD subjects (p1⁄4 0.36) and CSF BDNF within groups was not different among Met-BDNF genotypes. CSF BDNF concentration decreased with age among older normals and was higher in women than men (both p < 0.001). Neither presence of APOE e4 allele (p 1⁄4 0.33) nor Met-BDNF genotype (p 1⁄4 0.09) was related to CSF BDNF levels.After adjusting for age, gender, education, CSF Ab42 and tau, and APOE and BDNF genotypes, lower CSF BDNF concentration was associated with poorer Immediate and Delayed Paragraph Recall at baseline (both p< 0.05) and greater decline in paragraph recall scores and Category Fluency at approximately 3 years of follow-up (both p<0.01). Conclusions: Decline in CSF BDNF concentration was a feature of advancing age. This decline was independent of CSF Ab42 and tau, biomarkers of preclinical AD, and was associated strongly with reduced performance in declarative memory tests and tests of executive function. Further reduction in CSF BDNF occurred in AD. Our data suggest that reduced secretion of BDNF in the central nervous system is one mechanism that may contribute to age-related cognitive decline.