November 05, 2007
Alzheimers Gene Lowers Childhood Cognitive Performance

The variation of apolipoprotein E known as apoE4 gene doesn't just increase the risk of Alzheimer's Disease. Carriers of the apoE4 genetic variant show differences in mental performance as children.

PORTLAND, Ore. - Children who possess a gene known to increase the risk of Alzheimer's disease already show signs of reduced cognitive function, an Oregon Health & Science University study has found.

Scientists in the OHSU School of Medicine discovered that 7- to 10-year-olds with a member of a family of genes implicated in development, nerve cell regeneration and neuroprotection display reduced spatial learning and memory, associated with later-life cognitive impairments.

Results of the study, presented today at Neuroscience 2007, the 37th annual meeting of the Society for Neuroscience in San Diego, suggest that changes predisposing a person to Alzheimer's and other forms of dementia might occur much sooner in the brain than previously thought.

"One of our questions has been is this a risk that only happens with age, or is it already - early on - the cause of differences in performance," said study co-author Jacob Raber, Ph.D., associate professor of behavioral neuroscience and neurology in the OHSU School of Medicine. "This study suggests there already are cognitive differences very early on in life."

The researchers looked at 55 kids aged 7 to 10.

"When we looked at non-demented healthy elderly, we saw the clear effect of apoE4," he said. "So it's not just Alzheimer's disease. ApoE4 carriers generally do worse in our tests. Among the nondemented oldest old, where the mean age is 82, those who have apoE4 do less well" on cognitive tests.

In their study on children, Raber and colleagues - lead author Summer Acevedo, Ph.D., OHSU postdoctoral fellow, and Byung Park, Ph.D., senior biostatistics associate in the OHSU Biostatistics & Bioinformatics Shared Resource - examined 55 healthy boys and girls ages 7 to 10. Among them were eight girls and six boys who carried the apoE4 gene, and 17 girls and 24 boys who didn't.

Quite a few leftists want us to accept as a matter of secular faith that genetic variants don't create substantial differences in intellectual performance. But the accumulating evidence unsurprisingly (after all, the mind is a manifestation of physical phenomena) says otherwise.

Falling costs and falling risks for starting pregnancies in vitro are probably going to lead many prospective parents to select against embryos that carry apoE4. What ambitious parent wants their son or daughter to do poorly on the "Memory Island" test? None I hope.

Raber, Acevedo and Park found that apoE4 carriers scored lower in location recognition tests, and non-apoE4 carriers outperformed apoE4 carriers in the "Memory Island" test by navigating closer to the visible target location. Also, non-apoE4 carriers showed spatial memory retention when a target wasn't present and searched more frequently for the targets in the appropriate quadrants while apoE4 carriers did not.

In all, 75.6 percent non-apoE4 carriers showed target preference compared with only 43 percent of apoE4 carriers.

I'd like to know the frequency of apoE4 as a function of social class, level of education, tested IQ, and income. Does apoE4 show up at lower frequency in smarter people?

I'd also like to know what advantage apoE4 confers that allowed it to become fairly frequent in human populations. One source on apoE4 frequencies in different populations puts it at 11.7% in Tyrolean Europeans, 37% in Khoi San blacks, and 4.9% in Chinese. In recent centuries has apoE4 experienced selective pressure against it?

Share |      Randall Parker, 2007 November 05 10:22 PM  Brain Genetics

Anders Sandberg said at November 6, 2007 3:43 AM:

apoE4 seems to be protective against childhood diarrhea:

Oriá RB, Patrick PD, Zhang H, Lorntz B, de Castro Costa CM, Brito GA, Barrett LJ, Lima AA, Guerrant RL., APOE4 protects the cognitive development in children with heavy diarrhea burdens in Northeast Brazil. Pediatr Res. 2005 Feb;57(2):310-6.

"We found a high frequency of APOE4 alleles (18% versus 9-11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (greater than or equal to the median of seven illnesses in the first 2 y of life), those with APOE4 did significantly better in the coding subtest (p=0.01) when compared with APOE4-negative children with similar diarrhea burdens. Positive correlations between the APOE4 occurrence and coding scores remained, even after adjusting for family income, maternal education, and breast-feeding. Moreover, the APOE4-positive group, under heavy burdens of diarrhea, had preserved semantic fluency and the mean difference in fluency scores, p=0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in favela children and suggest a protective role of the APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 y of life."

So a plausible explanation might be that apoe4 protects the brain during childhood disease (possibly at the price of developing really good cognitive function, but since childhood diarrhea damages cognition anyway this might be fitness-increasing). The authors develop this more in this paper:

Oriá RB, Patrick PD, Blackman JA, Lima AA, Guerrant RL. Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development. Med Hypotheses. 2007;68(5):1099-107.

drtomcor said at November 6, 2007 7:13 AM:

I would like to see data shown by frequency of both maternal and paternal genes. For example, ApoE4/4, 3/3, 3/4. ApoE2 is much less common. I think many normal people would be a 3/4 combination. Gene expression is also a key factor, not everyone with E4 gets Alzheimers, yet we know highly intelligent folks can get it. E4 persists because it has some value as paper above suggests. I would greatly prefer a vaccine for Alzheimers to aborting ApoE4 babies. I, or you, might be an E4!

HellKaiserRyo said at November 6, 2007 12:50 PM:

"I would greatly prefer a vaccine for Alzheimers to aborting ApoE4 babies. I, or you, might be an E4!"

What does this mean? Are you a member of the religious right? Of course, abortion isn't fun either.

Dragon Horse said at November 6, 2007 5:58 PM:

The Frequencies in populations are interesting

YCaucasians (Tyroleans) (Hallman et al., 1991)

Blacks(Khoi San) (Sandholzer et al., 1995)

Asians (Chinese) (Kao et al., 1995)

Alaskans (Scheer et al., 1995)

Amazonian Amerindians (present study)


On first glance it appears that Alaskans and Amerindians in the Amazon are pretty close as you would expect but then:











Being that Amerindians have much less genetic diversity than Europeans, and Europeans far far less than SSAfricans I wonder how divergent populations actually are in Africa (being the Khoisan are pretty distant from most living Africans) or how large a gap there is between Southern Slavs and people in England for example.

drtomcor said at November 6, 2007 6:06 PM:

"What does this mean?"

It means that people with an E4 gene are people we know and love. Maybe it is us. These are people who are on the whole, normal. They may have a susceptibility to Alzheimers, which we would strive to prevent or cure. I don't like the idea of aborting for this reason; there is too much potential for a great life. All life has risks, and the risks cannot all be predicted.

"Religious right?" What if I was(if I knew what that means)...would that permit you to make an automatic assumption about my comment?

My point is that I'm not in favor of ending a life that could be as high a quality as yours. I might if I knew Downs syndrome was on the way, or some others (Nieman-Pick, Tay-Sachs, muscular dystrophy).

MostlyAPragmatist said at November 6, 2007 6:10 PM:

"Quite a few leftists want us to accept as a matter of secular faith that genetic variants don't create substantial differences in intellectual performance."

Aww, man! I was loving this post and then you had to get political and ruin the ride. Why bring the politics of left/right into this? Now I have to worry about whether you're some right-wing crank.

In the future, if there are really "quite a few leftists" who deny a genetic component to intellect, just name one or two. As is, that sentence makes you sound a little paranoid.

Randall Parker said at November 6, 2007 6:11 PM:


Thanks a lot for that. This isn't surprising. Pathogens are one of the biggest selective pressures. We've got a number of alleles which confer disease resistance but at a cost. This looks like yet another one.

HellKaiserRyo said at November 6, 2007 6:43 PM:

""Religious right?" What if I was(if I knew what that means)...would that permit you to make an automatic assumption about my comment?

My point is that I'm not in favor of ending a life that could be as high a quality as yours. I might if I knew Downs syndrome was on the way, or some others (Nieman-Pick, Tay-Sachs, muscular dystrophy)."

There is a significant moral difference "killing" an embryo that carries (you said fetus however) ApoE4 or Down Syndrome, Duchenne muscular dystropy etc. than killing a child or an adult with it mainly because the latter can suffer while the other cannot. Also the latter possesses an interest to live.

drtomcor said at November 6, 2007 7:09 PM:


You need to pay more attention. The word fetus appears nowhere in my comments, until now. Actually I used the word "babies"; I used that to emphasize that ApoE4 genes are found in normal people. I guess "babies" is now a buzz word.

As for what is a significant moral difference, and who does or doesn't suffer, you ought to say it's your opinion, because that is all it is.

Randall Parker said at November 6, 2007 7:29 PM:


Christian fundamentalists deny the overwhelming evidence for the evolution of species. Leftists look down on them. But leftists effectively deny the overwhelming evidence for local selective pressures on brain genes. That is incredibly unscientific. Look at the recent reaction to James Watson. It was entirely unscientific.

MostlyAPragmatist said at November 7, 2007 2:53 AM:


His comments weren't made in a scientific forum--they were made in the Times. It is too much to expect they be treated scientifically in mass media. I honestly don't see a conflict between left/right here.

I think the world distanced itself from Watson's statement because he said he believed our social policies in Africa will fail because they are not as smart as us. That link between lower IQs in Africa and failure of our social plans to increase standard of living requires a lot of justification that he didn't provide. His statement is indistinguishable from saying "Africans aren't smart enough to know what's good for them." That might not be what he meant, but this isn't an intellectual tete a tete , it's a newspaper interview--he should have had his filters turned on.

Randall Parker said at November 7, 2007 8:03 PM:


Plenty of scientists offer their opinions on many scientific subjects (e.g. global warming) to The Times and many other publications. They do not prove their opinions and to prove such opinions isn't even possible in many cases. Plus, the number of words in a newspaper story aren't enough to prove anything anyway. What Watson did wasn't unusual at all except for the fact that his scientific opinions on race are heresy.

Basically, you seem to be arguing that one shouldn't voice a heresy until and unless one can prove it. Um, too many people have their filters on and too many people are in the closet as regards their views on this particular heresy. If everyone felt compelled to be honest tomorrow Watson would suddenly find himself in the company of a huge number of scientists on this topic. Some accomplished scientists agree with Watson who won't say so publically.

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