Why do neurodegenerative diseases such as Alzheimer’s affect only the elderly? Why do some people live to be over 100 with intact cognitive function while others develop dementia decades earlier?
More than a century of research into the causes of dementia has focused on the clumps and tangles of abnormal proteins that appear in the brains of people with neurodegenerative diseases. However, scientists know that at least one piece of the puzzle has been missing because some people with these abnormal protein clumps show few or no signs of cognitive decline.
A new study offers an explanation for these longstanding mysteries. Researchers have discovered that a gene regulator active during fetal brain development, called REST, switches back on later in life to protect aging neurons from various stresses, including the toxic effects of abnormal proteins. The researchers also showed that REST is lost in critical brain regions of people with Alzheimer’s and mild cognitive impairment.
“Our work raises the possibility that the abnormal protein aggregates associated with Alzheimer’s and other neurodegenerative diseases may not be sufficient to cause dementia; you may also need a failure of the brain’s stress response system,” said Bruce Yankner, Harvard Medical School professor of genetics and leader of the study.
“If true, this opens up a new area in terms of treatment possibilities for the more than 5 million Americans currently living with Alzheimer’s disease,” said Yankner, who in the 1990s was the first to demonstrate the toxic effects of amyloid beta, the hallmark abnormal protein in Alzheimer’s.