Researchers at King's College London have established a new blood-based test that can predict the risk of Alzheimer's disease up to 3.5 years prior to clinical diagnosis. Alzheimer's disease is a brain disorder that slowly destroys memory and thinking skills, the ability to carry out the simplest tasks, and worsens learning and organising skills because it causes the brain cells to die.
The study is based on the idea that components in human blood can modulate the formation of new brain cells. This process is called neurogenesis, and occurs in an important part of the brain called hippocampus.
The hippocampus is a complex brain structure embedded deep into the temporal lobe, plays a major role in learning and memory, is vulnerable, could get damaged by a variety of stimuli, and gets affected in several neurological and psychiatric disorders.
Alzheimer's disease affects the formation of new brain cells in the hippocampus during the early stages of the disease. However, previous studies have been able to study neurogenesis only in the later stages of Alzheimer's disease, through autopsies.
What is Mild Cognitive Impairment?
The researchers from King's College London collected blood samples over several years from 56 individuals with Mild Cognitive Impairment (MCI), in order to understand the early changes. MCI is a condition where someone will begin to experience a worsening of their memory or cognitive ability, language, or judgement, and is the stage between the expected decline in memory and thinking that happens with age and the more serious decline of dementia. While dementia is a general term used to describe a decline in mental ability, Alzheimer's is a specific brain disease.
The new study describing the findings was recently published in the journal Brain.
Link between MCI and Alzheimer’s disease
Not everyone experiencing MCI goes on to develop Alzheimer's disease. However, those with MCI progress to a diagnosis of Alzheimer's disease at a much higher rate than the wider population, the study said.
There were 56 participants in the study. Of these, 36 went on to have a diagnosis of Alzheimer's disease. This accounts for over 64 per cent of the total number of participants.
How the study was conducted
In a statement released by King's College London, Dr Aleksandra Maruszak, one of the joint first authors on the paper, said that in the study, the researchers treated brain cells with blood taken from people with MCI, exploring how those cells changed in response to blood as Alzheimer's disease progressed.
How did the circulatory system affect brain cells?
The researchers made important discoveries while studying how blood affected the brain cells. In the blood samples collected from participants over the years who subsequently deteriorated and developed Alzheimer's disease, a decrease in cell growth and division and an increase in apoptotic cell growth was observed. Apoptosis is the process by which cells are programmed to die. However, the samples were also observed to increase the conversion of immature brain cells to hippocampal neurons.
Neurogenesis could be an early compensating mechanism for neurodegeneration
The underlying reasons for the increased neurogenesis observed is unclear. However, the researchers believe that neurogenesis may be an early compensating mechanism for neurodegeneration, which refers to the loss of brain cells, and is experienced by those developing Alzheimer's disease.
What makes the study unique?
In the statement, Professor Sandrine Thuret, the lead author on the paper, 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 the researchers the idea of modelling the process of neurogenesis in a dish using human brain cells and human blood. In the study, the researchers aimed to use the model to understand the process of neurogenesis and to use changes in the process to predict Alzheimer's disease, she added.
The team found the first evidence in humans that the circulatory system of the body can have an effect on the brain's ability to form new cells.
Significance of the study
The researchers analysed the blood samples collected furthest away from when the participants were diagnosed with Alzheimer's disease and found that the changes in neurogenesis occurred 3.5 years prior to a clinical diagnosis.
Dr Edina Silajdžić, the joint first author on the paper, said the findings are extremely important, potentially allowing researchers to predict the onset of Alzheimer's early in a non-invasive fashion. She said this could complement other blood-based biomarkers that reflect the classical signs of Alzheimer's disease, such as the accumulation of amyloid and tau, which are the 'flagship' proteins of Alzheimer's disease.
In the statement, 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. One of the potential applications of the blood-based test used is that it can help stratify individuals with memory problems for a clinical trial of disease-modifying drugs for Alzheimer's.
According to the researchers, the findings could present an opportunity to further understand the changes the brain goes through at the earliest stages of Alzheimer's disease.