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A stylised graphic of an astrocyte attached to the axon of a neuron.

The paper, published in the journal Molecular Psychiatry, focuses on a type of star-shaped brain cell called astrocytes, which support the function of neurones. When the brain is under attack by a neurological disease, like Alzheimer’s disease, these astrocytes react to defend their neurones.

Therefore, measuring the reactivity of astrocytes in the brains of people with Alzheimer’s disease could be a way to examine the disease progression. But currently the most effective way to measure astrocyte reactivity is post-mortem, as the methods for living patients lack accuracy.

Now, this DPUK-funded study has confirmed that a chemical called 11C-BU99008 highlights the reactive astrocytes in the brains of people with Alzheimer’s disease when viewed using a PET brain scanner.

PET scanners use fluorescent dyes called tracers to reveal individual cells in the brain, with each tracer binding to a particular cell type. 11C-BU99008 is a tracer that this research team proved binds to reactive astrocytes, allowing researchers to see where in the brain they are.

The research team is led by Professor Paul Matthews, Head of the Department of Brain Sciences and the UK Dementia Research Centre at Imperial College London. Professor Matthews said: “In a world-first, our DPUK-funded collaborative study explored application to Alzheimer’s disease of a novel PET marker for activated astrocytes, the imidazoline-2-receptor ligand 11C-BU99008.”

The project was a proof-of-concept study, which is the process of confirming that ideas that work in animal models are applicable to humans before clinical trials are launched. It was funded by DPUK as part of its Experimental Medicine strand, which aims to generate new insights into the mechanisms underlying the development of dementia and give drug companies confidence to pursue particular treatments or lines of inquiry.

The research team found that people with cognitive impairment due to Alzheimer’s disease displayed more 11C-BU99008 in their brains than healthy ‘control’ participants, which indicates they had more reacting astrocytes. These astrocytes were mainly found in the frontal lobe of the brain, as well as the temporal lobes, where the memory centre is located, and the occipital lobe, which is responsible for vision.

The study also found that astrocyte reactivity is related to amyloid-beta plaques – clumps of protein thought to accumulate in the brains of people with Alzheimer’s disease. The researchers were able to show that people with more amyloid-beta in their brains also had a higher level of astrocyte reactivity.

But even the people with cognitive impairment who lacked amyloid-beta plaques had increased astrocyte reactivity, suggesting that astrocytes react first and may contribute to the formation of amyloid-beta plaques.

These important results pave the way for clinical studies investigating astrocyte reactivity as a target for potential new treatments for Alzheimer’s disease. This is especially exciting because reducing astrocyte reactivity could disrupt the formation of harmful amyloid-beta plaques, treating the disease process rather than its symptoms.

Professor Matthews concluded: “11C-BU99008 PET now adds to the toolkit researchers can use in evaluations of novel therapeutic molecules targeting damaging inflammatory responses in Alzheimer’s disease.  It opens a new window for observation of the earliest stages of Alzheimer’s disease.”

This promising research was also co-funded by GlaxoSmithKline and the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre.