by Alina He
Alzheimer’s disease (AD) is the most common form of dementia and affects an estimated 50 million worldwide (1). This devastating disease is characterized by a gradual cognitive decline, including impairments in memory and communication. Currently, there are no effective methods to prevent or treat the disease (2). In the brain, classical hallmarks of AD include plaques composed of accumulated beta-amyloid protein and widespread loss of nerve cells (3).
Nerve cells are born in a process called neurogenesis, which is mostly restricted to the developing brain. However, in the hippocampus, a key brain region for learning and memory, neurogenesis occurs throughout life (4). It has been reported that this adult neurogenesis is defective early on in animal models of AD and AD patients (5). Rudolph E. Tanzi’s team at Harvard University sought to determine if enhancing adult neurogenesis in the hippocampus could be a potential treatment strategy for AD and if the impairment of this neurogenesis contributes to AD progression (6). They used exercise, which is known to stimulate neurogenesis, and also genetic and pharmacological tools to directly manipulate neurogenesis in an AD mouse model and observed the effects on pathological features of the disease and performance on cognitive tasks.
They found that exercise reduced the amount of amyloid plaques and improved cognitive performance in AD mice. Neurogenesis activation was necessary for these exercise-induced cognitive benefits. However, increasing neurogenesis on its own was not enough to improve cognitive function. Exercise also led to increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, which is a protein that regulates cell survival, growth, and maturation, and is also known to play important roles in learning and memory (7). Remarkably, increasing both BDNF levels and neurogenesis enhanced cognitive function even without reducing amyloid plaques. The authors believe that cognition was ameliorated as a result of increased neurogenesis in a healthier cellular environment provided by BDNF.
On the other hand, decreasing neurogenesis early on worsened the loss of nerve cells and cognitive deficits in AD mice. This provides new evidence that suggests that impaired neurogenesis is involved in aggravating AD. The authors propose that the generation of hippocampal cells in adulthood is critical in maintaining the cell population, which becomes extremely vulnerable at later stages of the disease.
These findings reveal that exercise improved the cognitive outcomes of AD mice in a neurogenesis- and BDNF-dependent manner. Previous studies on the effects of exercise on the cognition of patients with dementia have yielded inconsistent conclusions (8-10). However, neurogenesis and BDNF levels were not assessed, so it is possible that some physical activity did not increase neurogenesis and/or BDNF expression enough to benefit cognition. A future line of investigation may include measuring exercise-induced changes in BDNF levels and neurogenesis in individuals with AD to further our understanding of its potential protective effects.
Excitingly, this research presents the future possibility of developing pharmacological agents to directly increase neurogenesis and BDNF levels in the hippocampus as a therapeutic strategy. Perhaps making new nerve cells in a healthier environment can combat the catastrophic death of cells and alleviate cognitive impairments in AD.