Scientists propose a new theory on Alzheimer's disease and amyloid connection

Worldwide, 50 million people live with Alzheimer's disease and other dementias. According to the Alzheimer's Association, in the United States, a person develops every 65 seconds this disease that causes problems of memory, thinking and behavior.

It has been more than 100 years since Alois Alzheimer, M.D., a German psychiatrist and neuropathologist, first reported the presence of senile plaques in the brain of a patient with Alzheimer's disease. This led to the discovery of an amyloid precursor protein that produces deposits or plaques of amyloid fragments in the brain, the alleged culprit of Alzheimer's disease. Since then, the precursor protein of amyloid has been the subject of numerous studies because of its association with Alzheimer's disease. However, the distribution of amyloid precursor proteins in and on neurons and its function in these cells remain unclear.

A team of neuroscientists led by the Brain Institute of Florida Atlantic University sought to answer a fundamental question in their fight against Alzheimer's disease: "Is the amyloid precursor protein the brain behind Alzheimer's disease or is she just an accomplice? "

Mutations in the precursor protein of amyloid have been associated with rare cases of familial Alzheimer's disease. Although scientists have gained much knowledge about the transformation of this protein into amyloid plaques, little is known about its native function in neurons. In the case of more common sporadic Alzheimer's disease, the highest genetic risk factor is a protein that mediates the transport of cholesterol and not this amyloid precursor protein. In addition, various clinical trials aimed at treating Alzheimer's disease by minimizing amyloid plaque formation have failed, including that of Biogen announced last month.

In a study published in the journal Neurobiology of the disease, Qi Zhang, Ph.D., lead author, researcher at the FAU Brain Institute and adjunct research professor at the FAU's Schmidt College of Medicine, with collaborators from Vanderbilt University, are attacking him at Mystery of Alzheimer's disease by designing a reporter for the amyloid precursor protein and to track the location and mobility of the protein using quantitative imaging with unprecedented accuracy.

For this study, Zhang and his collaborators genetically disrupted the interaction between cholesterol and the amyloid precursor protein. Surprisingly, by disengaging both, they discovered that this manipulation not only disrupted the trafficking of the amyloid precursor protein, but also harmed the distribution of cholesterol on the surface of neurons. Neurons with a modified distribution of cholesterol had swollen synapses, fragmented axons, and other early signs of neurodegeneration.

"Our study is intriguing because we have noticed a particular association between the precursor protein of amyloid and cholesterol that resides in the cell membrane of synapses, points of contact between neurons and biological basis of learning and of memory, "said Zhang. "The amyloid precursor protein may well be one of the many accomplices contributing in part to cholesterol deficiency." Strangely, the heart and brain seem to end up in the fight against bad cholesterol. "

Given the great involvement of cholesterol in almost every aspect of neuron life, Zhang and his collaborators have proposed a new theory on the precursor protein linkage of amyloid in Alzheimer's disease, particularly at the surface of these tiny synapses, which triggers neurodegeneration.

"While this cutting-edge research by Dr. Zhang and his collaborators at Vanderbilt University is still in its infancy, it could have implications for the millions of people at risk or with the disease. Alzheimer's, "said Randy D. Blakely, Ph.D., executive director of the FAU Brain Institute and professor of biomedical sciences at the FAU's Schmidt College of Medicine. "The number of people aged 65 and over with Alzheimer 's disease in Florida alone is expected to increase by 41.2% by 2025 to 720,000 people, which highlights the number of people living with Alzheimer' s disease. urgency to find a medical solution. "

At the local level, Alzheimer's disease affects 11.5% of Medicare beneficiaries in Palm Beach County and 12.7% of Medicare beneficiaries in Broward County (an increase of almost 18% over national average).

According to the Alzheimer's Association, Florida is the number one case of per capita Alzheimer's disease in the United States.