Recent work by Boston University School of Medicine researchers shows developments in a new model for the biology of Alzheimer’s disease, which could lead to entirely new approaches in treating the disease. Alzheimer’s disease disrupts one’s cognitive abilities, including memory, thinking, and behavior. It accounts for 60-80% of all dementia cases. The neurodegenerative disease is caused by clumps and accumulations of 2 proteins –beta-amyloid and tau– which cause nerve cell injury and in turn, dementia.

Comparison of a normal brain (left) and the brain of a person diagnosed with Alzheimer’s (right).

Recent work by the BUSM researchers has shown that the clumping and accumulation of the tau protein are largely due to stress. The accumulation of tau produces “stress granules” (RNA/protein complexes). The brain responds to these stress granules by producing important protective proteins. However, with excessive stress, there is a greater accumulation of stress granules, which in turn leads to greater accumulation of clumped tau, which causes nerve cell injury. In this study, researchers are using this model to show that reducing the level of stress granules could lead to improved nerve cell health. It may be possible to reduce the level of stress granules by genetically decreasing TIA1, a protein required for stress granule formation.

In an experimental model of Alzheimer’s disease, the research team found that reducing the TIA1 protein led to striking improvements in memory and life expectancy. However, although stress granule levels decreased (leading to better protection), the team observed that the clumps of tau became larger. The researchers further looked at the tau pathology and found that the while small clumps of tau (known as tau oligomers) are toxic, larger tau clumps are generally less toxic. According to pharmacology and experimental therapeutics professor Benjamin Wolozin, this discovery would explain why the experimental models experienced better memory and longer life expectancy. The implications and ability of TIA1 protein reduction in order to provide protection may lead to further novel developments in the biology and treatment of Alzheimer’s disease.


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