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APOE4 Points to NHE6 Inhibition as a Potential Means to Slow the Early Onset of Alzheimer's Disease

APOE4 Points to NHE6 Inhibition as a Potential Means to Slow the Early Onset of Alzheimer's Disease

19

Dec

2018

19

Dec



2018

APOE4 Points to NHE6 Inhibition as a Potential Means to Slow the Early Onset of Alzheimer’s Disease

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Why do people with the APOE4 variant of APOE have a much greater risk of Alzheimer’s disease? Past work has focused on its role in accelerating amyloid-β accumulation by disrupting recycling mechanisms in some way. Evidence is provided here for the relevant mechanisms to trace back to the acidity of the environment within parts of the cellular recycling system which APOE operates. APOE4 is more prone to dysfunction in that environment than is the case for other APOE variants. Manipulating the regulators of acidicity may thus enable Alzheimer’s disease to be slowed down at its very earliest stage – though the size of that effect in patients is a question mark. It seems plausible that it will have little effect on people with variants other than APOE4, for example.



ApoE is a lipid and cholesterol carrying protein that is primarily produced by the liver and is responsible for plasma lipid homeostasis. It occurs in three major isoforms in humans known as ApoE2, ApoE3 and ApoE4, with ApoE3 being the most frequent allele (~77% homozygosity) followed