Why APOE4 gene increases Alzheimer's risk

  • Synapses in Alzheimer's brains found to be clogged with clusterin and amyloid-beta proteins, and APOE4 carriers had more protein clumps than those without the gene variant.
  • APOE4 decreases activity in hippocampus that is critical for memory consolidation.
  • Study of Amazonian hunter-gatherers show APOE4 gene can provide benefits when exposure to parasites is high.

Alzheimer's gene linked to damage to brain connections

A study has found that synapses in people who had died with Alzheimer's contained clumps of clusterin and clumps of amyloid beta. These protein clumps may be damaging the links between neurons.

Those with the APOE4 gene had more clusterin and amyloid beta clumps than people with Alzheimer's without the risk gene. Those without dementia symptoms had less of the damaging proteins in their synapses.

https://www.eurekalert.org/pub_releases/2019-06/uoe-dsl062719.php

Alzheimer's gene impairs memory consolidation by disrupting brainwaves

A mouse study has found that the apoE4 protein decreases two types of brain activity in the hippocampus that are important for memory formation: sharp wave ripples (ripples) and coincident slow gamma activity. During the ripples, prior experiences are replayed numerous times to help preserve the memory of them, and the slow gamma activity that occurs during the ripples helps to ensure that the replay of those memories is accurate.

Mice with apoE4 had fewer ripples than mice with the normal apoE3 protein, and they had less slow gamma activity during the ripples. It appears that apoE4 expression disrupts slow gamma activity during ripples, and this in turn impairs memory consolidation.

The finding points to restoring slow gamma activity in the hippocampus as a therapeutic target.

http://www.eurekalert.org/pub_releases/2016-05/gi-glt050516.php

APOE4 gene benefits those with high parasite exposure

In response to those wondering why we have this gene variant if it's so damaging, a study looked at how the ApoE gene might function differently in the more infectious environment of our hunter-gatherer ancestors. It found that Amazonian forager-horticulturalists who carried ApoE4 and had a high parasitic burden displayed steadier or even improved cognitive function compared to non-carriers with a similar level of parasitic exposure.

For Tsimane ApoE4 carriers without high parasite burdens, the rates of cognitive decline were more similar to those seen in industrialized societies.

ApoE4 has previously been shown to eliminate some infections like giardia and hepatitis. Other studies have shown potential benefits of ApoE4 in early childhood development

https://www.eurekalert.org/pub_releases/2016-12/asu-adc122916.php

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