You are here

Scientists investigate fundamental Alzheimer’s question

Scientists investigate fundamental Alzheimer’s question
25th April 2019

Neuroscientists at Florida Atlantic University's (FAU) Brain Institute set themselves the task of investigating one of the most fundamental questions in Alzheimer’s disease research. They wanted to know whether amyloid precursor protein is the mastermind behind Alzheimer's disease or is it just an accomplice?

It’s a conundrum that goes back over a century and began when a German psychiatrist by the name of Alois Alzheimer first reported the presence of senile plaques in patients’ brains. This led to amyloid precursor protein being discovered in the brain.

Ever since, scientists have believed amyloid precursor protein could be the cause of Alzheimer’s disease, but this has not been proven unequivocally. Despite extensive studies, its distribution and role remains unclear.

Various studies have shown how the protein turns into amyloid plaques, but its native function in neurons is elusive. While it is known mutations in the amyloid precursor protein have a link to familial Alzheimer’s disease, this form of the condition is very rare.

In the much more common sporadic Alzheimer’s disease, it is a different protein that provides the highest genetic risk factor. It is responsible for cholesterol transportation and not this amyloid precursor protein.

As Alzheimer’s is one of the biggest challenges in modern medicine, researchers across the world are looking for ways to combat it. A number of clinical trials aiming to prevent the formation of amyloid plaques have failed, however, as this fundamental question remains unanswered.

This is where the team from FAU, led by Qi Zhang, have stepped in, as they worked alongside colleagues from Vanderbilt University to find a solution. They devised a multifunctional reporter for amyloid precursor protein that can track the location and mobility of the protein through quantitative imaging better than ever before.

To carry out the research, the team disengaged the cholesterol and amyloid precursor proteins. By not interacting with each other, they found that the trafficking of amyloid precursor protein and cholesterol distribution at the neuronal surface were both disrupted.

When the neurons had their distribution of cholesterol altered, they exhibited swollen synapses and fragmented axons, as well as other early signs of neurodegeneration. This has enabled the team to propose a new theory on the role of precursor protein in Alzheimer's disease.

Dr Zhang said: "Our study is intriguing because we noticed a peculiar association between amyloid precursor protein and cholesterol that resides in the cell membrane of synapses, which are points of contact among neurons and the biological basis for learning and memory.
"Amyloid precursor protein may just be one of the many accomplices partially contributing to cholesterol deficiency. Strangely, the heart and brain seem to meet again in the fight against bad cholesterol."

More research needs to be done, but this latest breakthrough could help to pave the way for better treatment for Alzheimer’s in the future. It’s predicted that by 2025, one million people in the UK will be living with the condition and there is currently no cure.