Alzheimer’s disease is a progressive neurodegenerative disorder with no 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 a person with MCI is to develop Alzheimer’s disease.

Scientists at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) 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 human blood can modulate the formation of new brain cells, a process called neurogenesis.

Neurogenesis of the hippocampus in adults is crucial for learning and memory and is affected early in Alzheimer’s disease. Exploring a proxy of how the systemic milieu influences hippocampal neurogenesis could serve as an early biomarker for the course of Alzheimer’s disease, as the systemic environment of the circulatory system influences hippocampal neurogenesis.

Scientists collected blood samples from 56 individuals with mild cognitive impairment (MCI) over several years to understand the early changes. While not everyone who experiences MCI develops Alzheimer’s disease, those with the condition develop a diagnosis much more quickly than the rest of the population. Of the 56 participants in the study, 36 were diagnosed with Alzheimer’s disease.

Dr. Aleksandra Maruszak, one of the joint first authors of King’s IoPPN, explains: “In our study, we treated brain cells with blood from people with MCI, examining how those cells changed in response to blood as Alzheimer’s disease progressed.”

The scientists discovered several important findings during their research into the impact of blood on brain cells. Blood samples taken over time from people who later became ill and developed Alzheimer’s disease stimulated a reduction in cell growth and division and an increase 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.

While the exact causes of the increased neurogenesis are still unknown, scientists theorize it could be an early defense against the neurodegeneration (loss of brain cells) that occurs in people who develop Alzheimer’s disease.

Professor Sandrine Thuret, the lead author of the King’s IoPPN study, said: “Previous studies have shown that blood from young mice can have a rejuvenating effect on the cognition of older mice by enhancing hippocampal neurogenesis. That is how we came up with the idea of ​​modeling the process of neurogenesis in a dish using human brain cells and human blood.”

“In our study, we wanted to use this model to understand the process of neurogenesis and use changes in this process to predict Alzheimer’s disease. We found the first evidence in humans that the body’s circulation can affect the brain’s ability to form new cells.”

The increase in neurogenesis started 3.5 years before a clinical diagnosis, according to the findings, when the scientists examined only the blood samples furthest from when the participants were diagnosed with Alzheimer’s disease.

Dr. Edina Silajdžić, the study’s joint first author, added: “Our findings are extremely important, potentially allowing us to predict early onset of Alzheimer’s disease in a non-invasive way. This could complement other blood-based biomarkers that reflect the classic 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 larger and more diverse group of people. We’re excited about the potential applications of the blood-based test we’ve been using. For example, it could help stratify individuals with memory problems for a clinical trial of disease-modifying drugs for Alzheimer’s disease.”

Scientists noted, “These findings may provide an opportunity to further understand the changes the brain goes through in the earliest stages of Alzheimer’s disease.”

Magazine reference:

  1. Aleksandra Maruszak et al. Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum. Brain, awac472, DOI: 10.1093/brain/awac472