Bone-derived neurotrophic factor (BDNF) is a circulating signal molecule know to produce neuroprotective effects, aiding neurons to resist stress. It may be involved in supporting some of the functions of neurons. Further, it encourages neurogenesis, the production of new neurons from neural stem cell populations and their integration into existing neural circuits. This is essential for memory, learning, and what little capacity for regeneration exists in the central nervous system. More circulating BDNF produces more neuroprotection, more neurogenesis, better defense against the aging of the brain. Today's open access paper provides one example from the many lines of evidence to support this assertion.
From what is presently known, BDNF appears to be one of a short list of circulating signal proteins for which increased levels (presumably up to some safe upper bound) produce effects that are near all beneficial. Others include α-klotho, follistatin, and VEGF. Circulating proteins with this characteristic are good targets for long-lasting gene therapies that can make use of proven, low-cost technologies. One can use a single fat pad injection of a small amount of even an inefficient gene therapy vector, such as off-patent AAV serotypes or PEI conjugated plasmids, to transduce enough cells to make a difference. The transduced cells become factories for the production of the desired signal molecule, and that production can last for years to decades.
Serum BDNF and progression to MCI in cognitively normal older adults: A prospective cohort study
Brain derived neurotrophic factor (BDNF) is the most abundant and extensively researched neurotrophin in the mammalian brain. It protects neurons from stress and neurotoxicity, and supports neurogenesis, development, and differentiation of neurons. Furthermore, BDNF production and signaling are associated with neurophysiological processes such as long-term potentiation (LTP). During the aging process, BDNF levels increase in response to oxidative stress, providing partial antioxidant defense.
In humans, directly measuring BDNF levels in the brain is challenging. Instead, BDNF levels in blood are used as a proxy, as supported by animal studies demonstrating that BDNF can cross the blood-brain barrier bidirectionally and that peripheral and central BDNF levels are closely associated. Regarding human studies, higher blood BDNF levels have been associated with a slower rate of cognitive decline in Alzheimer's disease, and a reduced risk of conversion to dementia. However, it remains uncertain whether blood BDNF levels are associated with the risk of progression to mild cognitive impairment (MCI), which is considered as a pre-dementia state or a high risk stage of dementia, in cognitively normal (CN) individuals. Given that various modifiable lifestyle factors, including physical and cognitive activities, and dietary habits, can increase blood BDNF levels, elucidating the association between BDNF levels and progression to MCI is very meaningful in terms of the prevention of late-life cognitive decline.
In this study, we aimed to investigate whether higher serum BDNF levels are associated with a reduced likelihood of progressing to MCI over a four-year follow-up period in CN older adults. Longitudinal analyses were conducted using follow-up data from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study. Among the 274 participants, 26 developed MCI during follow-up. The high BDNF group had a significantly lower incidence of MCI compared to the low BDNF group (hazard ratio , 0.27. This association persisted even after adjusting for BDNF Val66Met polymorphism, amyloid PET positivity, vascular risk factors, cholesterol levels, triglycerides, homocysteine, BMI, smoking, alcohol, TBI history, CES-D, and MMSE scores (HR, 0.14). Subgroup analyses further revealed that the association was significant only in women, individuals younger than 75 years, those with less than a college degree, and amyloid PET-negative individuals.
These findings suggest a protective role of BDNF against clinical progression to MCI in cognitively healthy older individuals. This effect appears to be more prominent in women, as well as in relatively younger, less educated, and amyloid PET-negative individuals.
View the full article at FightAging
