Dementia study links gene with damage to brain connections

Summary: Post mortem examinations of brain tissue from Alzheimer’s patients revealed synapses contained clumps of clusterin, in addition to amyloid beta. The clumps were more abundant in those with genetic risk factors from Alzheimer’s disease.

Source: University of Edinbugh

Brain tissue from people with Alzheimer’s showed that a protein called clusterin builds up in vital parts of neurons that connect cells and may damage these links.

Brain tissue from people with Alzheimer’s showed that a protein called clusterin builds up in vital parts of neurons that connect cells and may damage these links.

Scientists say the findings shed light on the causes of the disease and will help to accelerate the search for a treatment.

The study, led by Professor Tara Spires-Jones at the University of Edinburgh, focused on synapses – connections between brain cells that allow the flow of chemical and electrical signals. These signals are vital for forming memories and are key to brain health, experts say.

Researchers showed that synapses in people who had died with Alzheimer’s contained clumps of clusterin, which could contribute to dementia symptoms. These synapses also contained clumps of amyloid beta, the damaging protein that is found in the brains of people with Alzheimer’s.

People with a common risk gene, called apolipoprotein E4, had more clusterin and amyloid beta clumps in their synapses than people with Alzheimer’s without the risk gene.

Those without dementia symptoms had even less of the damaging proteins in their synapses.

The discovery was made using powerful technology that allowed the scientists to view detailed images of more than one million synapses. Individual synapses are around 5000 times smaller than the thickness of a sheet of paper.

Synapse loss in Alzheimer’s disease was previously established, but the clumping of damaging proteins together in synapses was unknown until now because of difficulties in studying them due to their tiny size.

Alzheimer’s disease is the most common form of dementia, affecting around 500,000 people in the UK. It can cause severe memory loss and there is no cure.

dna is shown here
People with a common risk gene, called apolipoprotein E4, had more clusterin and amyloid beta clumps in their synapses than people with Alzheimer’s without the risk gene. The image is in the public domain.

Professor Spires-Jones, Programme Lead at the UK Dementia Research Institute at the University of Edinburgh, said: “We have identified another player in the host of proteins that damage synapses in Alzheimer’s disease. Synapses are essential for thinking and memory, and preventing damage to them is a promising target to help prevent or reverse dementia symptoms. This work gives us a new target to work towards in our goal to develop effective treatments.”

Funding: The study was funded by the European Research Council and the UK Dementia Research Institute. The UK DRI is funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. It is published in the journal Brain Communications.

About this neuroscience research article

Source:
University of Edinbugh
Media Contacts:
Guy Atkinson – University of Edinbugh
Image Source:
The image is credited to Journal of Neuroscience.

Original Research: Open access
“Clusterin accumulates in synapses in Alzheimer’s disease and is increased in apolipoprotein E4 carriers”. Rosemary J Jackson, Jamie Rose, Jane Tulloch, Chris Henstridge, Colin Smith, Tara L Spires-Jones.
Brain Communications. doi:10.1093/braincomms/fcz003

Abstract

Clusterin accumulates in synapses in Alzheimer’s disease and is increased in apolipoprotein E4 carriersy

One of the major challenges in developing effective therapeutic strategies for Alzheimer’s disease is understanding how genetic risk factors contribute to neurodegeneration. The apolipoprotein epsilon 4 isoform (APOE4) and variants in the Clusterin (CLU) gene (also known as apolipoprotein J) are associated with increased risk of developing Alzheimer’s. Our previous work demonstrated that APOE4 exacerbates synapse degeneration and synaptic accumulation of toxic oligomeric amyloid beta in human Alzheimer’s and mouse models of disease. Here we observe clusterin in synapses in human AD brain. The percentage of synapses containing clusterin is higher in APOE4 carriers than APOE3 carriers. Furthermore, we observe oligomeric amyloid beta accumulation within synapses containing clusterin which is also higher in APOE4 carriers. These data link two genetic risk factors with synapse degeneration in Alzheimer’s and support a potential role for clusterin working with APOE in causing synaptic damage.

Feel free to share this Neuroscience News.
Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.