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New test could detect Alzheimer's disease 3.5 years before clinical diagnosis - King's College London

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27 January 2023
New test could detect Alzheimer's disease 3.5 years before clinical diagnosis
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.

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27/6/23, 23:43 New test could detect Alzheimer's disease 3.5 years before clinical diagnosis - King's College London

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.

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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.

“
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.

Dr Aleksandra Maruszak, one of the study’s joint first authors from King’s IoPPN

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.

“
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
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27/6/23, 23:43 New test could detect Alzheimer's disease 3.5 years before clinical diagnosis - King's College London

evidence in humans that the body’s circulatory system can have an effect on the brain’s
ability to form new cells.

Professor Sandrine Thuret, the study’s lead author, King’s IoPPN

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.

“
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 Edina Silajdžić, the study’s joint first author, King’s IoPPN

“
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.

Dr Hyunah Lee, the study’s joint first author, King’s IoPPN

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27/6/23, 23:43 New test could detect Alzheimer's disease 3.5 years before clinical diagnosis - King's College London

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.
In this story

Sandrine Thuret
Professor of Neuroscience

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