Hippocampus and Alzheimer's: new data

A gene associated with Alzheimer's disease weakens memory by disrupting the reproduction system in the hippocampus

LifeSciencesToday based on Gladstone Institutes: Gene Linked to Alzheimer's Disease Impairs Memory by Disrupting Brain's “Playback System”

Scientists from the Gladstone Institutes have established how the most important genetic risk factor for Alzheimer's disease - a pathological variant of the apolipoprotein E gene – causes memory loss. Mice with this variant of apoE have a specific type of brain activity that is important for repeated reproduction of a new experience, which adversely affects its memorization.

Present in the genome of 65-80% of patients with Alzheimer's disease, the ApoE4 gene encodes a protein of the same name that significantly increases the risk of developing this neurodegenerative disease. In a new study published in the journal Neuron, scientists have found that the ApoE4 protein alters the activity of neurons in the hippocampus, an important memory center seriously affected by Alzheimer's disease. In this area, ApoE4 reduces the activity of two types of brain waves that are important for storing the experience in memory: pointed pulsating waves, or pulsating ripples (sharp wave ripples) and slow gamma waves flowing simultaneously with them. During the pulsating ripples, the previous experience is replayed many times to help keep it in memory, and the slow gamma waves that occur during the ripples help to guarantee the accuracy of this reproduction.

"When we encounter something new, the cells of the hippocampus are excited, in a certain order. Later, the same cells are excited again and again in the same order, reproducing the event, which helps to consolidate memory, and we do not forget this experience," explains the first author of the article Anna Gillespie (Anna Gillespie), PhD. "The excitation of these cells is organized by slow gamma waves that occur during ripples. If these waves are disrupted, reproduction is disorganized, compromising memory."

Mice with ApoE4 had fewer pulsating ripples than animals with normal protein (apoE3), and fewer slow gamma waves during ripples. After receiving these results, scientists wondered whether these differences in brain activity affect the ability to remember and reproduce information stored in the brain.

To answer it, the researchers conducted experiments on mice expressing ApoE4 in all cells except the inhibitory neurons of the hippocampus. From an earlier study, they knew that such mice showed no signs of death of inhibitory neurons in the hippocampus and there was no impairment in the ability to learn and remember. In this study, mice showed normal slow gamma waves despite fewer ripples. It follows from this that slow gamma waves - the coordination of cell excitation during reproduction – seem to be the most important factor in memory consolidation, more important than the number of reproductions during ripples.

Our study suggests that disruption of slow gamma waves during ripples is one of the main consequences of ApoE4 expression, which probably impairs memory consolidation," says study leader Yadong Huang, MD, PhD. "Knowing this, we can now continue our work towards correcting and restoring slow gamma waves in the hippocampus to prevent or mitigate memory loss in Alzheimer's disease."

Article by Gillespie et al. Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples published in the journal Neuron.

Portal "Eternal youth" http://vechnayamolodost.ru  12.05.2016