Saturday, January 13, 2007

APOE4: a blessing and a curse   posted by amnestic @ 1/13/2007 11:04:00 PM

The APOE gene comes in a number of varieties in humans. The ancestral primate allele (APOE4) still hangs out in humans at a low frequency and is most famous for increasing risk for Alzheimer's. I noted a paper a few months back suggesting that the APOE4 allele is protective for severe childhood diarrhea. I just found another paper showing an association between APOE4 and better episodic memory. So you have better memory when you're young, but you pay for it when you get older. It seems like learning was just easier for APOE4 carriers. In the fMRI portion of the study they showed reduced hippocampal signal, interpreted as "more efficient" use of neural resources. The authors note that the memory phenotypes of humans are paralleled by LTP phenotype in an APOE4-carrying transgenic mouse strain. LTP is enhanced in young mice, but gets worse as they get old. Apparently, APOE4 is capable of stimulating CREB activation unlike other alleles. CREB is a heavily studied transcription factor thought to be important for inducing expression of genes needed for memory consolidation. At one point, the authors seem to suggest that this ability might help explain the greater hippocampal efficiency in APOE4 carriers, but the whole transcriptional activation and cellular consolidation program involving CREB is supposed to take several hours if not a whole day, while the changes in hippocampus activity took place within an hour. So maybe better LTP induction could be part of the explanation, but I doubt CREB is part of the equation. I wonder if the pattern of memory performance (young = above avg.; old = below) can be observed regardless of APOE genotype. Maybe this is more mechanical such that if your memory system is overclocked you are likely to burn it out.