Points toward mechanism of age-onset toxicity of Alzheimer's protein
.
Alzheimer's Donation
Donate Online Now
.

Like most neurodegenerative diseases, Alzheimer's disease usually appears late in life, raising the question of whether it is a disastrous consequence of aging or if the toxic protein aggregates that cause the disease simply take a long time to form.
Now, a collaboration between researchers at the Salk Institute for Biological Studies and the Scripps Research Institute shows that aging is what's critical. Harmful beta amyloid aggregates accumulate when aging impedes two molecular clean-up crews from getting rid of these toxic species.

New model for neurodegenerative diseases

Half of all people who reach age 85 will likely be affected by Alzheimer's disease, and the onset age – usually around 75 – is almost the same for all sporadic neurodegenerative aggregation diseases. Thus, Salk researchers have developed a model that explains why these disorders diseases occur late in life.Throughout life, brain cells produce aggregation-prone beta-amyloid fragments that must be cleared. "This process is very efficient when we are young but as we get older it gets progressively less efficient," says Cohen. As the affected individual reaches the seventh decade of life the clearance machineries fail to degrade the continually forming toxic aggregates and the disease emerges. In individuals who carry early onset Alzheimer's-linked mutation, an increased "aggregation challenge" leads to clearance failure and the emergence of Alzheimer's much earlier – usually during their fifth decade."It was very satisfying when the biochemical data from Jeffery's lab and genetic results from our lab came together," recalls Dillin. Both scientists are continuing the collaboration by searching for small molecules that delay the aging program and boost protective mechanisms.Other contributing authors were co-lead author Jan Bieschke, Ph.D., formerly at Scripps and now at Max Delbrueck Center in Berlin, and research assistant Rhonda M. Perciavalle.