Researchers from Rush University have linked higher gene expression of brain-derived neurotrophic factor (BDNF) to a reduced rate of cognitive decline, suggesting that it may play a role in the attenuation of Alzheimer’s disease (AD) pathology.
Previous research has tied low levels of BDNF to more rapid cognitive decline. Within the central nervous system, BDNF is thought to be involved in angiogenesis, neurogenesis, and cellular interactions that are important in complex behaviors and cognition. BDNF expression may also be suppressed by β-amyloid.
Aron S. Buchman, MD, of the Alzheimer’s Disease Center at Rush University Medical Center in Chicago, and colleagues conducted annual cognitive assessments in 535 older adults (average age 81.4 years at baseline, 88.5 years at death; mean follow-up = 6.3 years) followed by brain autopsy upon death to assess the impact of BDNF gene expression on cognitive decline and its association with AD pathology. Overall, greater BDNF gene expression was found to be associated with slower cognitive decline (P<0.001). This association was found to be strongest in those with dementia (P=0.003). After adjusting for demographics, the researchers found that those in the 90th percentile of BDNF gene expression experienced cognitive decline nearly 50% slower than those in the lowest 10%.
Participants with evidence of AD pathology had lower expression of BDNF (P=0.006), however the effects of plaques and tangles on cognitive decline was reduced for those with high levels of BDNF expression. Those that had both the greatest level of AD pathology and BDNF expression (90th percentile) demonstrated a 40% slower decline in cognition than those with a lower level of BDNF expression (10th percentile).
“This relationship was strongest among the people with the most signs of Alzheimer’s disease pathology in their brains,” Dr Buchman said in a statement. “This suggests that a higher level of protein from BDNF gene expression may provide a buffer, or reserve, for the brain and protect it against the effects of the plaques and tangles that form in the brain as a part of Alzheimer’s disease.”
In an accompanying editorial, Michal Schnaider Beeri, PhD, of the Department of Psychiatry at the Icahn School of Medicine in New York, and Joshua Sonnen, MD, of the Department of Pathology at the University of Utah Medical Center in Salt Lake City, UT, note that the research “may have substantive clinical implications, since slower rate of cognitive decline may postpone major AD-related negative outcomes, from patient and family suffering, to institutionalization and early death,” however it is not clear from the data that BDNF is solely responsible for the slower rate of cognitive decline.
The authors note that exercise has previously been shown to increase serum BDNF levels; however the relationship between BDNF levels in the blood and in the brain is not clear. They suggest that BDNF’s impact on cognition may be related to counteraction of pathology through synaptic plasticity and neurogenesis.
“More research is needed to confirm these findings, determine how this relationship between protein produced by BDNF gene expression and cognitive decline works and see if any strategies can be used to increase BDNF in the brain to protect or slow the rate of cognitive decline,” said Dr Buchman.
- Buchman AS, Yu L, Boyle PA, Schneider JA, De Jager PL, Bennett DA. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology. 2016; doi:10.1212/WNL.0000000000002387.
- Beeri MS, Sonne J. Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. Neurology. 2016; doi:10.1212/WNL.0000000000002389.