Not just plaques
The precursor of beta-amyloid (Amyloid precursor protein, APP) is well known for its important role in the development of Alzheimer's disease, but its significance for healthy brain functioning, on the contrary, remained largely unknown. An international research team led by molecular biologist Professor Ulrike Muller from Heidelberg University, Germany, obtained new data on the physiological functions of the APP protein family using a mouse model devoid of it. Researchers have shown that the lack of APP during development leads to defects in important areas of the brain involved in learning and memory. These mice had severe learning disabilities and autistic behavior.
Alzheimer's disease develops due to the accumulation of insoluble protein plaques in the brain around nerve cells. These plaques consist mainly of small β-amyloid peptides (Aß), which are the product of APP cleavage. Aß peptides damage nerve cells, eventually leading to their death. According to the researchers, the non–pathological role of APP is also worth studying, given the fact that this protein, like two other closely related proteins, is produced by most nerve cells in the brain - especially those involved in learning and memory formation.
The absence of APP leads to an abnormal arrangement of neurons (yellow) in the hippocampus. Neurons devoid of APP family proteins exhibit fewer synaptic connections.
Mueller's research team used mice as a model organism that were genetically modified in such a way as to block the production of all three proteins of the APP family. A thorough study of their brains showed that the lack of APP in the process of brain development led to abnormalities in the structure of the hippocampus – the most important area of the brain for memory formation. The researchers noted a violation of neuronal transmission and a decrease in the number of synaptic connections. APP deficiency was also associated with a significant deterioration in communication between neurons and seriously affected the results of behavioral tests evaluating learning.
The researchers noted that these disorders in brain development led to behavioral changes that are similar to autistic disorders. The mice showed typical repetitive movements and a lack of interest in social interactions with other mice.
Thus, the APP family plays an important role in the normal development of the nervous system, learning, memory formation and social communication. Perhaps these data will help in the development of new treatments for Alzheimer's disease.
Article V. Steubler et al. Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning and causes an autism-like phenotype published in EMBO Journal.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on materials from Heidelberg University: Alzheimer's protein APP regulates learning and social behavior in the healthy brain.