Role of Alzheimer's Protein is Deciphered!

New insights on the physiological functions of the amyloid precursor protein (APP – plays a key role in Alzheimer's disease) has been gained by using a mouse model lacking APP as per a study led by molecular biologist Prof. Dr. Ulrike Müller from Heidelberg University.

Alzheimer's disease (AD) is a neurodegenerative disease that leads to gradual memory loss and behavioral changes. It is characterized by the formation of beta-amyloid plaques in the brain tissues, years before the actual symptoms occur.

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‘New insights on the physiological functions of the APP protein family (which plays a key role in Alzheimer's disease) have been unraveled by using a mouse model lacking APP. This Alzheimer protein APP is found to regulate learning and social behavior in the healthy brain.’

These small β-amyloid peptides (Aβ), occur as a cleavage product of the amyloid precursor protein (APP) which triggers the aggregation of insoluble protein deposits in the brain. Although the detrimental effect of Aβ peptides on neurons has been recognized for many years, little is known about the natural physiological functions of APP.

To analyze the non-pathological perspective of these proteins particularly in critical regions for learning and memory formation and in the development and functionality of the nervous system, the study team used mice as a model organism, which had been genetically engineered to block the production of all APP family proteins.

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It was found that the absence of APP during brain development was shown to result in the malformation of important brain regions – the layered structure of the hippocampus that is essential for memory formation and learning. Hence the mice that were severely impaired in their learning abilities also exhibited autistic-like behavior.

"We observed that the absence of APP led to impaired neuronal wiring and a decrease in the number of synaptic connections. It also greatly reduced communication between nerve cells and severely affected the animal's performance in behaviour tests that assess learning," says Ulrike Müller, who heads the department of Functional Genomics at the Institute of Pharmacy and Molecular Biotechnology of Heidelberg University.

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The study highlighted the fact that these disruptions in brain development that gave rise to autistic-like behaviors, had revealed recurring movement patterns and lack of interest in social interactions with other mice.

"Our findings suggest that the APP family plays a crucial role in the normal development of the nervous system, learning, memory formation and social communication. In the future, these understandings may aid the development of novel therapeutics for Alzheimer's disease," says, Professor Müller.

Source-Medindia