What causes neuron death in Alzheimer’s Disease

Washington – Researchers have said that massive neuron death that occurs in Alzheimer’s Disease (AD) seems to be caused by raw ingredients of plaques and tangles working in concert, rather than by plaques and tangles themselves.

However, George Bloom, Ph.D., and colleagues at the University of Virginia (UVA), said that a novel group of proteins, Rac1, Gas (Gs alpha) and NCAM, and two protein kinase complexes, mTORC1 and mTORC2, play a role in driving mature neurons to their death.

Dr. Bloom said that he views AD as fundamentally a problem of the cell cycle, with both amyloid-beta and tau required for the interaction that pushes neurons into destructive CCR.

He said that the massive neuron death that occurs in AD therefore appears to be caused by the raw ingredients of plaques and tangles working in concert with each other, rather than by the plaques and tangles themselves.

Dr. Bloom and lab members Andres Norambuena and Lloyd McMahon’s identification reveals how a fundamental balance is upset, placing neurons on the road to AD.

Dr Bloom said that the mTOR complexes are master regulators of cellular proliferation, growth and metabolism, asserting that most important, their results indicate that tau normally inhibits mTOR from promoting neuronal cell replication, but that this inhibition is reversed by an amyloid beta oligomer-induced, mTOR-dependent mechanism that modifies tau. In other words, tau and mTOR regulate each other.

This delicate balance is compromised by amyloid-beta oligomers in a way that allows neurons that should never replicate to re-enter the cell cycle. They fail to divide and eventually die instead.