Health & Medicine, Canada (Commonwealth Union) – A groundbreaking study conducted by the University of Toronto’s (U of T’s) Tanz Centre for Research in Neurodegenerative Diseases sheds new light on the impact of somatostatin, a hormone, during the initial phases of Alzheimer’s disease. This research challenges conventional beliefs and offers fresh insights into the role of somatostatin in the early development of the disease.
In a significant breakthrough, Gerold Schmitt-Ulms, a co-author of the study published in Scientific Reports, emphasizes the newfound importance of somatostatin in Alzheimer’s disease. The research demonstrates, for the first time, the extent of somatostatin’s impact. It is revealed that somatostatin does not completely prevent the aggregation of amyloid beta protein but rather decelerates its accumulation. This discovery holds great significance, although the implications for treatment are yet to be fully understood. Schmitt-Ulms, an investigator at the Tanz Centre and a professor in the University of Toronto’s department of laboratory medicine and pathology. He further indicated that they were uncertain what it meant for treatment.
The prevailing theory regarding the initiation of Alzheimer’s disease, known as the amyloid cascade hypothesis, posits that an excess production of amyloid beta protein leads to the formation of oligomers (small clumps composed of varying numbers of amyloid beta monomers). These oligomers subsequently accumulate, forming larger plaques that inflict damage upon neurons.
In the 1970s, researchers noticed that individuals with Alzheimer’s disease exhibited lower levels of somatostatin hormone in their brains compared to those without the condition. Additionally, it was observed that the characteristic amyloid beta plaques tended to develop near neurons that produce somatostatin. These observations hinted at a potential connection between somatostatin and the aggregation of amyloid beta, although the precise nature of this relationship remained elusive.
Progress was made in the early 2000s when a Japanese research team published findings indicating that somatostatin stimulates the production of an enzyme known as neprilysin, which plays a role in breaking down amyloid beta. This discovery suggested that reduced levels of somatostatin would lead to a decline in neprilysin, impairing the degradation of amyloid beta. Consequently, the plaques would continue to grow, perpetuating the progression of Alzheimer’s disease.
The knowledge in regards to the part played by somatostatin is where the field remained for over a decade.
In a previous investigation, Gerold Schmitt-Ulms and his research team focused on the monomer and oligomer forms of amyloid beta, aiming to identify brain molecules capable of binding to the toxic oligomeric forms. Remarkably, they discovered that somatostatin, among all the proteins present in the brain, exhibited the smallest size yet demonstrated exceptional selectivity in its binding to amyloid beta, specifically interacting with the oligomers.
Furthermore, their observations unveiled that somatostatin impeded the formation of oligomers, and this effect was more pronounced with higher concentrations of somatostatin. This pioneering study provided the initial evidence indicating a direct interaction between somatostatin and the oligomeric forms of amyloid beta, which are recognized as the earliest stages of Alzheimer’s disease. These findings presented an alternative perspective on the influence of somatostatin in the context of the disease.
“We didn’t actually intend to work on somatostatin, but these results made us very curious about what would happen if somatostatin was absent in an animal model that was genetically engineered to develop amyloid beta aggregations,” said Schmitt-Ulms.
The findings of this study have not only challenged the traditional understanding of somatostatin’s role in Alzheimer’s disease but have also sparked discussions within the scientific community. However, the implications of these findings for treatment strategies remain uncertain.
Somatostatin serves significant functions in various systems such as the gastrointestinal, endocrine, and nervous systems. Therefore, selectively enhancing its role in inhibiting amyloid aggregation would pose considerable challenges. Additionally, it remains unclear whether augmenting somatostatin levels to halt the growth of amyloid beta aggregates would be beneficial in treating the disease, as further research is needed to determine its potential therapeutic value.
