Researchers from the Gladstone Institute of Neurological Disease and the University of California, San Francisco have found that the natural brain protein apolipoprotein E3 (apoE3) prevents memory problems associated with Alzheimer's disease.
Study findings in a transgenic mouse model showed that high levels of amyloid proteins in the brain lead to memory impairment and that apoE3 can inhibit the detrimental amyloid effects. Findings also showed that apoE4, a variant of the apoE3 protein, does not provide this protection.
A report on the findings appears in the new issue (March 23) of the journal Nature.
Previous research has shown that people with the apoE4 gene develop Alzheimer's (AD) more often and earlier than those who inherit the apoE3 gene, and the new findings help explain this genetic link.
Other investigations in the AD field have previously identified amyloid proteins as having a key role in development of AD, but the new research by the GIND/UCSF team provides the first direct evidence that apoE3 can help prevent memory deficits induced by amyloid proteins, while apoE4 cannot.
Further research will now explore why apoE3 preserves normal memory function so much better than apoE4, according to Lennart Mucke, MD, senior study investigator, director of the GIND, and UCSF professor of neurology. Understanding this difference could lead to the development of new drugs that simulate the protective quality of apoE3 and in turn prevent the devastating effects of AD, he said.
Jabob Raber, PhD, GIND staff research scientist and UCSF assistant professor of neurology, was first author of the study. Co-investigators were Derek Wong, BS; Gui-Qui Yu, MS; Manuel Buttini, PhD; Robert W. Mahley, MD, PhD; and Robert Pitas, PhD.
The research was supported by grants from the National Institute on Aging, the Alzheimer's Association, and the John Douglas French Alzheimer's Foundation.
Journal
Nature