Alzheimer’s disease is a progressive neurodegenerative condition without effective treatment options. Individuals diagnosed with mild cognitive impairment (MCI) are known to progress to Alzheimer’s disease at a significantly higher rate.
However, not all individuals with MCI develop Alzheimer’s disease. This highlights the need to accurately estimate how likely an individual with MCI is to progress to Alzheimer’s disease.
Scientists from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London have developed a new blood-based test that detects Alzheimer’s disease 3.5 years before clinical diagnosis. The study supports the idea that components in the human blood can modulate the formation of new brain cells, a process termed neurogenesis.
Adult hippocampal neurogenesis is crucial for learning and memory, and it is affected early in Alzheimer’s disease. Examining a proxy of how the systemic milieu impacts hippocampus neurogenesis could serve as an early biomarker for the course of Alzheimer’s disease because the circulatory systemic environment influences hippocampal neurogenesis.
Scientists collected blood samples over several years from 56 individuals with Mild Cognitive Impairment (MCI) to understand the early changes. While not everyone experiencing MCI develops Alzheimer’s disease, those with the condition progress to a diagnosis at a much higher rate than the wider population. Of the 56 participants in the study, 36 received a diagnosis of Alzheimer’s disease.
Dr. Aleksandra Maruszak, one of the study’s joint first authors from King’s IoPPN, explains, “In our study, we treated brain cells with blood taken from people with MCI, exploring how those cells changed in response to blood as Alzheimer’s disease progressed.”
The scientists uncovered several significant findings while researching the impact of blood on brain cells. Blood samples taken throughout time from people who later became ill and developed Alzheimer’s disease stimulated a reduction in cell growth and division and an upsurge in apoptotic cell death (the process by which cells are programmed to die). The scientists did see that these samples accelerated the maturation of immature brain cells into hippocampal neurons, though.
Although the exact causes of the increased neurogenesis are yet unknown, scientists theorize that it could be an early defense against the neurodegeneration (loss of brain cells) that occurs in people developing Alzheimer’s disease.
Professor Sandrine Thuret, the study’s lead author from King’s IoPPN, said, “Previous studies have shown that blood from young mice can have a rejuvenating effect on the cognition of older mice by improving hippocampal neurogenesis. This gave us the idea of modeling the process of neurogenesis in a dish using human brain cells and human blood.”
“In our study, we aimed to use this model to understand the process of neurogenesis and to use changes in this process to predict Alzheimer’s disease. We found the first evidence in humans that the body’s circulatory system can affect the brain’s ability to form new cells.”
The increases in neurogenesis began 3.5 years before a clinical diagnosis, according to the findings when the scientists only examined the blood samples taken the furthest from when the participants were given an Alzheimer’s disease diagnosis.
Dr. Edina Silajdžić, the study’s joint first author, added, “Our findings are extremely important, potentially allowing us to predict onset of Alzheimer’s early in a non-invasive fashion. This could complement other blood-based biomarkers that reflect the classical signs of the disease, such as the accumulation of amyloid and tau (the ‘flagship’ proteins of Alzheimer’s disease).”
Dr. Hyunah Lee, the study’s joint first author, said, “It is now essential to validate these findings in a bigger and more diverse group of people. We are excited about the potential applications of the blood-based test we used. For example, it can help stratify individuals with memory problems for a clinical trial of disease-modifying drugs for Alzheimer’s.”
Scientists noted, “These findings could present an opportunity to further understand the changes the brain goes through at the earliest stages of Alzheimer’s disease.”
- Aleksandra Maruszak et al. Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum. Brain, awac472, DOI: 10.1093/brain/awac472