How studying these twelve Alzheimer’s patients with no symptoms could help doctors cure the memory-robbing disease
Researchers intrigued by people with features of Alzheimer’s disease – but none of the symptoms – have been examining their brains in the search for a cure.
They initially took samples from the Dutch Brain Bank, a repository of brains from more than 5,000 people who have died from a neurological disease.
They were shocked when twelve of them showed signs of Alzheimer’s disease but were still cognitively healthy.
They found that people with certain changes in their brains linked to the disease showed important differences that could protect against Alzheimer’s disease.
Their research paves the way for more research into what exactly causes the difference between the resilient group, and provides new clues for developing effective treatments.
Among the thousands of donated brains collected in the study, researchers found that 12 people had signs of Alzheimer’s disease in their brains, but no associated cognitive impairment. Structural and chemical changes in the brain, such as cell death, affect a person’s level of cognitive decline
Alzheimer’s disease affects approximately 47 million people worldwide and approximately 5.8 million in the US.
The U.S. estimate is expected to rise in coming years as the country’s population continues to age.
The Dutch researchers identified several differences between the brains of people with Alzheimer’s disease, but no symptoms, compared to people with symptoms.
The brain with the disease but no cognitive decline was called ‘resilient’.
Dr. Luuk de Vries, first author of the study, said: ‘We think that genetics and lifestyle play an important role in resilience, but the exact mechanism is still unknown.’
Their hope is that additional research will uncover the specific genetic variants that can make a person more resilient to disease, which could guide researchers in developing highly targeted treatments that target specific gene mutations.
Some gene mutations can affect certain processes, such as energy production for energy cells.
Dr. deVries said: ‘If we can find the molecular basis for resilience, we will have new leads for the development of medicines that can activate processes related to resilience in Alzheimer’s patients.’
Genes can influence the production of a protective antioxidant called metallothionein, which protects the brain from free radicals.
People with Alzheimer’s disease but no symptoms also had fewer immune cells that specifically target pathogens that enter the central nervous system.
These cells become overactive when certain toxic proteins, amyloid beta and tau, build up in the brain.
This causes inflammation that can damage nerve cells and cause brain tissue to shrink, both hallmarks of Alzheimer’s disease.
They also noticed important differences in the way proteins folded and clumped together in the people involved in the study who had symptomatic Alzheimer’s, versus the asymptomatic people with Alzheimer’s disease.
The team then found evidence that resilient brains may be better at clearing away toxic proteins and waste that can lead to brain shrinkage.
Most Alzheimer’s treatments that have passed regulatory approval, such as Lequembi, target amyloid protein aggregation, but so far none have been shown to significantly improve cognitive function.
But a better understanding of the chemical underpinnings of cell death that lead to cognitive decline could give drug developers and researchers a new, better way to attack disease biomarkers such as tau tangles.
Their research was published in the journal Acta Neuropathologica Communications .