Worldwide, 50 million people are living with Alzheimer's and other dementias. According to the Alzheimer's Association, every 65 seconds someone in the United States develops this disease, which causes problems with memory, thinking and behavior.
It has been more than 100 years since Alois Alzheimer, M.D., a German psychiatrist and neuropathologist, first reported senile plaques in an Alzheimer's patient brain. This led to the discovery of the amyloid precursor protein, which produces deposits or plaques of amyloid fragments in the brain, the alleged perpetrator of Alzheimer's disease. Since then, the amyloid precursor protein has been extensively studied for its association with Alzheimer's disease. However, the distribution of the amyloid precursor proteins within and on the neurons and their function in these cells remains unclear.
A team of neuroscientists led by the Brain Institute of Florida Atlantic University attempted to answer a fundamental question in the search for Alzheimer's disease: "Is amyloid precursor protein the mastermind behind Alzheimer's disease or is it just an accomplice?
Mutations in the amyloid precursor protein have been associated with rare cases of familial Alzheimer's disease. Although scientists have learned a great deal about how this protein turns 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 involved in cholesterol transport rather than this amyloid precursor protein. In addition, various clinical trials to combat Alzheimer's disease have failed by minimizing the formation of amyloid plaques, including one from Biogen, which was announced last month.
In a study published in the journal study [Neurobiologie der Krankheit] [QiZhangPhDLeitenderAutorErmittleramBrainInstitutederFAUundeinAssistenzprofessoramSchmidtCollegeofMedicinederFAUsowieMitarbeiterderVanderbiltUniversitysetzensichmitdiesemAlzheimer-RätselauseinanderindemereinenmultifunktionalenReporterfürAmyloidPrecursorProteinentwickeltundLokalisierungundMobilitätdesProteinsmittelsquantitativerBildgebungmitbeispielloserGenauigkeit
For the study, Zhang and his colleagues disrupted the interaction between cholesterol and amyloid precursor protein genetically. Surprisingly, by deactivating the two, they discovered that this manipulation not only interferes with the trade in amyloid precursor protein, but also interferes with the cholesterol distribution at the neuronal surface. Neurons with altered cholesterol distribution exhibited swollen synapses and fragmented axons and other early signs of neurodegeneration.
"Our study is intriguing because we have found a special relationship between the amyloid precursor protein and the cholesterol that lies in the cell membrane of the synapses are points of contact between neurons and the biological basis for learning and memory," Zhang said. "Amyloid precursor protein may just be one of the many accomplices that contribute in part to cholesterol deficiency, and strangely enough, the heart and brain seem to meet again in the fight against bad cholesterol."
Given the broad participation of cholesterol in almost all areas of life of neurons, Zhang and his associates have proposed a new theory about the association of amyloid precursor proteins in Alzheimer's disease, especially in the surface of these tiny synapses the neurodegeneration triggers.
"Although this research is still at an early stage Dr. Zhang and his staff at Vanderbilt University could affect the millions of people with Alzheimer's disease or suffering from it," said Randy D. Blakely, Managing Director of the FAU Brain Institute and Professor of Biomedical Science at the FAU's Schmidt College of Medicine. "The number of people in Florida aged 65 and over who suffer from Alzheimer's is expected to increase by 41.2% to an estimated 720,000 by 2025, underscoring the urgency of a medical breakthrough."
Alzheimer's suffers 11.5% from Medicare beneficiaries in Palm Beach County and 12.7% from Medicare beneficiaries in Broward County (an increase of nearly 18% compared to the national average).
According to the Alzheimer's Association, Florida is number one in the United States in per capita cases of Alzheimer's disease
Researchers answer many decades of questions about proteins found in Alzheimer's brain plates
Claire E. DelBove et al. Reciprocal modulation between amyloid precursor protein and cholesterol of the synaptic membrane, demonstrated by live cell imaging, Neurobiology of Disease (2019). DOI: 10.1016 / j.nbd.2019.03.009
Scientists propose new theory of Alzheimer's amyloid connection (2019, April 23)
accessed April 23, 2019
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