It pinpoints mitochondria, the organelles within cells designed to turn glucose into energy, as a key site that specific fragments of a particular form of apoE attack, leading to the neuronal death characteristic of Alzheimer's disease (AD).

The findings are published online by the Proceedings of the National Academy of Science, in advance of publication in the December 20, 2005, issue of PNAS.

According to Gladstone Assistant Investigator Yadong Huang, MD, PhD, who headed the study, it has been known for several years that a correlation exists between lowered glucose metabolism and the presence in the brain of a mutant form of a protein that transports cholesterol.

Scientists have been unable to determine if this mutant protein actually interferes with the ability of neurons to make use of glucose in the brain, but they have theorized that such an inability to access glucose might kill off crucial brain cells, causing AD symptoms.

The devastating effects of AD are well known: progressive and inexorable loss of cognitive function that erases memories, extinguishes personality, and robs people of their ability to think, reason and carry out the activities of everyday life. Despite intensive efforts to identify the underlying causes, and considerable progress in unraveling the web of contributing factors, the pathogenesis of AD remains tantalizingly elusive, and a cure is still out of reach, says Huang.

Seeking answers to a fundamental question in AD research on what actually causes brain cells to die in affected patients, Huang and his scientific team pursued a particularly promising avenue of research over the last few years. Their efforts focused on apoE, a protein comprised of 299 amino acids whose apoE4 isoform has be
'"/>

Contact: John Watson
jwatson@gladstone.ucsf.edu
415-734-2019
Gladstone Institutes
14-Dec-2005