Alzheimer’s disease can start anywhere in the body before traveling to the brain, alarming new research has found.
Researchers at the University of British Columbia in Canada found the toxic proteins that lead to the neurodegenerative illness can develop in the liver or even kidneys before invading grey matter.
The discovery could lead to drugs that target dementia in organs that are much easier to treat – years before the onset of symptoms.
Lead author, psychiatrist Professor Weihong Song, said: ‘Alzheimer’s disease is clearly a disease of the brain. But we need to pay attention to the whole body to understand where it comes from – and how to stop it.’
Researchers have found Alzheimer’s-linked proteins in the kidneys and liver (file image)
Alzheimer’s, the most common form of dementia, has long been assumed to originate in the brain.
But this new research indicates it could be started by breakdowns elsewhere.
The study published in Molecular Psychiatry offers hope of developing drugs that could stop or slow the disease without acting directly on the brain.
This is a complex, sensitive and often hard-to-reach organ because of the blood-brain barrier.
This restricts the passage of substances from blood circulating in the body to other fluids in the brain – a vital mechanism to maintain normal mental function.
The downside is many drugs that may have the potential to treat dementia would not work in the brain.
But now they could go to work in the kidney or liver – ridding the blood of a rogue protein before it ever reaches the brain.
This cancer-like mobility was demonstrated through a technique called parabiosis – surgically joining two lab animals so they share the same blood supply for months.
The researchers attached normal mice – which don’t naturally develop Alzheimer’s – to peers modified to carry a mutant human gene that produces high levels of amyloid-beta.
In Alzheimer’s patients this protein ultimately forms clumps – or ‘plaques’ – that destroy brain cells and lead to symptoms of memory loss and confusion.
The normal mice that had been joined to genetically engineered partners for a year ‘contracted’ Alzheimer’s.
Professor Song said the amyloid-beta travelled from the genetically-modified mice to the brains of their normal partners where it accumulated and began to inflict damage.
ALZHEIMER’S: FAST FACTS
WHAT IS IT?
Alzheimer’s disease is a progressive, degenerative disease of the brain.
A build-up of abnormal proteins causes nerve cells to die.
This disrupts the transmitters that carry messages, and causes the brain to shrink.
As brain cells die, the functions they provide are lost.
That includes memory, orientation and the ability to think and reason.
The progress of the disease is slow and gradual.
On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.
- Loss of short-term memory
- Behavioral changes
- Mood swings
- Difficulties dealing with money
- Difficulties making a phone call
- Difficulties following a TV show
- Severe memory loss, forgetting close family members, familiar objects or places
- Becoming anxious and frustrated over inability to make sense of the world…
- …This can lead to aggressive behavior
- Eventually lose ability to walk
- May have problems eating and drinking
- The majority will eventually need 24-hour care
HOW ALZHEIMER’S DIFFERS FROM NORMAL MEMORY LOSS:
With ordinary age-related forgetfulness, you will still remember details associated with the thing they’ve forgotten.
For example, you may forget your neighbor’s name in conversation, but you still know that person is your neighbor.
Alzheimer’s sufferers forget the entire context.
Not only did the normal mice develop plaques but also a pathology similar to ‘tangles’ – twisted protein strands that form inside brain cells.
This disrupted their function and eventually killed them from the inside-out.
Other signs of Alzheimer’s-like damage included brain cell degeneration, inflammation and micro-bleeds.
In addition, the ability to transmit electrical signals involved in learning and memory – a sign of a healthy brain – was impaired, even in mice that had been joined for only four months.
Besides the brain amyloid-beta is produced in blood platelets, blood vessels and muscles – and its precursor protein is found in several other organs.
But until the experiments it was unclear if amyloid-beta from outside the brain could contribute to Alzheimer’s.
Professor Song, chair of Canada Research in Alzheimer’s, and neurologist Prof Yan-Jiang Wang, of Third Military Medical University in Chongqing, China, said their study shows it can.
Prof Song said: ‘The blood-brain barrier weakens as we age.
‘That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration.’
He foresees a drug that would bind to amyloid-beta throughout the body – tagging it biochemically in such a way that the liver or kidneys could clear it.
Prof Song and Prof Wang said amyloid-beta plays a ‘pivotal role’ in Alzheimer’s but although it’s believed it originates in the brain itself it’s also generated by peripheral tissues.
They said: ‘Our study is the first to reveal blood-derived amyloid-beta can enter the brain, form the related pathologies and induce functional deficits of neurons.
‘Our study provides novel insight into Alzheimer’s disease pathogenesis and provides evidence that supports the development of therapies by targeting amyloid-beta metabolism in both the brain and the periphery.’
Prof Song and Prof Wang added: ‘Amyloid-beta is thought to be mainly generated by neurons in the brain.
‘However, it’s also generated outside the brain in appreciable quantities in platelets, skeletal muscle and vascular walls.
‘We found circulating amyloid-beta levels are associated with the functions of peripheral organs including the liver, kidneys and lungs.
‘A recent study found amyloid-beta aggregates were present in the hearts and impaired heart function of patients with Alzheimer’s disease.
‘Thus, it is necessary to pay our attention to the whole body to understand disease pathogenesis and to develop therapies by targeting amyloid-beta metabolism in both the brain and the periphery.’
About 850,000 people in the UK have dementia – a figure that will rise to 2 million by 2050 because of the ageing population – and 5.5 million have the disease in the United States.