New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has established a blood-based test that could be used to predict the risk of Alzheimer’s disease up to 3.5 years before clinical diagnosis.
The study, published in the journal Brain, supports the idea that components in the human blood can modulate the formation of new brain cells, a process termed neurogenesis. Neurogenesis occurs in an important part of the brain called the hippocampus that is involved in learning and memory.
While Alzheimer’s disease affects the formation of new brain cells in the hippocampus during the early stages of the disease, previous studies have only been able to study neurogenesis in its later stages through autopsies.
To understand the early changes, researchers collected blood samples over several years from 56 individuals with Mild Cognitive Impairment (MCI), a condition where someone will begin to experience a worsening of their memory or cognitive ability. While not everyone experiencing MCI goes on to develop 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 went on to receive 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.”
In studying how blood affected the brain cells, the researchers made several key discoveries. The blood samples collected from participants over the years who subsequently deteriorated and developed Alzheimer’s disease promoted a decrease in cell growth and division and an increase in apoptotic cell death (the process by which cells are programmed to die). However, the researchers noted that these samples also increased the conversion of immature brain cells to hippocampal neurons.
While the underlying reasons for the increased neurogenesis remain unclear, the researchers theorise that it may be an early compensating mechanism for the neurodegeneration (loss of brain cells) experienced by those 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 modelling 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 and found the first evidence in humans that the body’s circulatory system can have an effect on the brain’s ability to form new cells.”
When the researchers used only the blood samples collected furthest away from when the participants were diagnosed with Alzheimer’s disease, they found that the changes in neurogenesis occurred 3.5 years prior to a clinical 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.”
The researchers say that these findings could present an opportunity to further understand the changes the brain goes through at the earliest stages of Alzheimer’s disease.
This study was possible thanks to funding from the John and Lucille van Geest Foundation, the Medical Research Council UK, the Cohen Charitable Trust, the Galen and Hilary Weston Foundation and the Rhodes Trust.
For more information, please contact Patrick O’Brien (Senior Media Officer)
Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum (DOI10.1093/brain/awac472) (Aleksandra Marusza, Hyunah Lee, Edina Silajdžić, Tytus Murphy, Benjamine Liu, Liu Shi, Chiara de Lucia, Abdel Douiri, Evgenia Salta, Alejo J. Nevado, Charlotte E. Teunissen, Pieter J. Visser, Jack Price, Henrik Zetterberg, Simon Lovestone, and Sandrine Thuret) was published in Brain.
When the embargo lifts, a copy of the paper will be found at the following address - https://bit.ly/3H9ahEF
About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience
King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.
www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn
The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation. https://mrc.ukri.org/
Method of Research
Subject of Research
Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum
Article Publication Date
Part of the work presented here is subject to a patent application GB1616691.0 with AM, TM, JP, SL, and ST listed as inventors. JP is a consultant at ReNeuron. BL is CEO and co-founder of Trialspark. SL is currently an employee of Janssen-Cilag. In the past 3 years he has provided consultancy to Eisai, SomaLogic and Merck and is a co-founder and director at CRISTAL Health. HZ has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies and CogRx, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The other authors declare no competing interests