SAN FRANCISCO, CAOCT. 13, 2010 -- Alzheimer's disease (AD) is an extremely complicated disease. Several proteins seem to be involved in its cause and progression. For example, the lipid-transport protein apolipoprotein E4 (apoE4) is the major genetic risk factor for AD, and apoE4 carriers account for 65% of all Alzheimer's cases, but exactly how apoE4 contributes to the disease is unclear.
Scientists at the Gladstone Institutes of Neurological Disease (GIND) have provided new insights into how apoE4 might be involved. In a study published today online in the Journal of Neuroscience, researchers led by led by Yadong Huang, MD, PhD, reported that apoE4-dependent learning and memory deficits are caused by loss of a specific type of neuron in the learning and memory center of the brain.
"We found that mice that had been genetically engineered to produce human apoE4 lost a specific kind of cells and that loss of these cells correlated with the extent of learning and memory deficits," said Yaisa Andrews-Zwilling, PhD, postdoctoral fellow and lead author of the study.
Those key cells are called GABAergic interneurons in the hilus of the hippocampus, an area of the brain involved in learning and memory and affected by AD. GABA is an important neurotransmitter released from GABAergic interneurons. As one component of a delicately balanced system for regulating brain activity, GABA functions to inhibit brain activity. AD brains seem to have low levels of GABA.
"Importantly, apoE4 causes GABAergic interneuron loss and learning and memory deficits in the absence of Ab peptide accumulation, a widely suspected toxin in Alzheimer's disease," said Dr. Huang, senior author of the study. "This demonstrates clearly that apoE4 plays Ab-independent roles in Alzheimer's disease."
To try to overcome the decrease of GABAergic interneuron function, the Gladstone team treated the apoE4 mice with daily injections of pent
|Contact: Valerie Tucker|