By Rebecca Fleeman
Alzheimer’s disease is the 6th leading cause of death in the United States. Over 5 million Americans suffer from Alzheimer’s disease, and even more alarmingly, there are no medications to stop or slow the progression of the disease. Alzheimer’s is characterized by a loss of neurons resulting in symptoms of reduced cognition and memory. While other cell types need to constantly regenerate (e.g. skin cells) throughout our lifetime, neurons have classically been thought to halt production in young adulthood when the brain is fully developed. Therefore, regeneration of neurons could be key to discovering a path to cure Alzheimer’s disease.
In the past 10 years, a few studies have identified neurogenesis (the creation of neurons) in adult stages of mice, primates, and humans. However, it is unclear at what age adult neurogenesis stops, and, more importantly, if Alzheimer’s disease patients lack this regenerative mechanism in neurons. In June of 2019, Tobin et al. published a study in the journal Cell Stem Cell which put this idea to the test. Postmortem brain tissue from humans over the age of 80 were analyzed to see if the neurons expressed proteins that are primarily found in newly made neurons. The researchers looked at cognitive continuum of postmortem brains from humans who were cognitively normal, had mild cognitive impairment (MCI), or had Alzheimer’s disease. Remarkably, they found all three types of brains contained neurons which expressed markers of neurogenesis. While the Alzheimer’s brains showed the presence of proteins required for neurogenesis, their levels where notably lower than neurogenesis-associated proteins in cognitively normal brains. The authors also noted that between individuals of similar cognitive levels, there was great variability in neurogenesis. This finding may help to explain why symptom severity can be inconsistent in patients with Alzheimer’s disease—patients with greater neuronal loss are more likely to show greater cognitive impairment.
So, what is the next step? How can scientists translate these results to finding a therapeutic that will prevent, slow, or even reverse Alzheimer’s disease? First, these results will need to be reproduced. While Tobin et al. were able to show that neurons express proteins typical of newly made, immature neurons, scientists are not sure this evidence of neurogenesis confirms the ability of immature neurons to develop into completely functional neurons in older adults. Understanding the potential for neurogenesis in vivo will be essential to understanding Alzheimer’s disease and other forms of neurodegeneration which plague an aging society.
- Tobin MK, Musaraca K, Disouky A, et al. Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients. Cell Stem Cell. 2019;24(6):974-982.e3. doi:10.1016/j.stem.2019.05.003