Abstract
Background
In non-demented older adults carriage of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) loss over 36 months. The extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g., serum) is unknown. The aim of this study was to determine the effect of Aβ+ and the BDNF Val66Met polymorphism on levels of serum mature BDNF (mBDNF), EM and HV volume at baseline and over 18-months in non-demented older adults.
Methods
Non-demented older adults (n=446) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18-months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+.
Results
At baseline, compared to the Aβ- group, the Aβ+ group showed significantly worse EM impairment and lower levels of serum mBDNF. Groups did not differ on HV at baseline. BDNF Val66Met polymorphism did not significantly affect serum mBDNF levels, EM performance or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant moderate decline in EM (d=0.28) and HV (d=0.42) but not serum mBDNF levels (d=0.02). Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant and moderate decline in EM (d=0.32) and HV (d=0.56) over 18-months but showed no change in serum mBDNF levels (d=0.02).
Conclusions
In Aβ+ Met carriers, there is substantial EM decline and HV loss over relatively short time intervals. However, there was no relationship between BDNF Val66Met polymorphism and serum mBDNF levels at baseline or over 18-months. Thus, while allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF and clinical phenotypes such as EM and HV in preclinical AD.