Alzeimer's and Amerindian population

Alzheimer's disease (AD) or senile dementia is a disease that, in a world with an ageing population is growing quickly. A study published in biorxiv.org: Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years, (2015) Hang Zhou et al., looked into the roots of this disease.

The study finds that "signals of brain evolution in AMH [Anatomically Modern Humans] are strongly related to Alzheimer’s disease pathways." in other words, the genetic changes that led to our advanced brain, as we evolved into modern H. sapiens, also led to our susceptibility to Alzheimer's.

Humans are the only species known to develop Alzheimer's; (AD) the disease is absent even in our closest living relatives, the chimpanzees.

Another paper by Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. (2013), The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013 Jan;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007., gives us an idea of the prevalence of the disease among modern human populations:

"...metaanalysis to estimate the prevalence and numbers of those affected, aged ≥60 years in 21 Global Burden of Disease regions.
RESULTS:
Age-standardized prevalence for those aged ≥60 years varied in a narrow band, 5%-7% in most world regions, with a higher prevalence in Latin America (8.5%), and a distinctively lower prevalence in the four sub-Saharan African regions (2%-4%). It was estimated that 35.6 million people lived with dementia worldwide in 2010, with numbers expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. In 2010, 58% of all people with dementia lived in countries with low or middle incomes, with this proportion anticipated to rise to 63% in 2030 and 71% in 2050."

Which is rather surprising, if we suffered a bottleneck when we left Africa (according to the OOA theory), most diversity should be found there, in Africa, and the genes that lead to Alzheimer's should prevail there too... but no, it is lowest in Africa and highest in... America, not in the US where you may expect some other external factor at work, no, it was found to be highest among Latin Americans, a mix that has a very high content of Amerindian genes.

But Zhou et al. find Negative Selection (NS) highest among Africans (YRI) compared to Chinese (CHB) or Europeans (CEU): "Regarding the NS signals, a much higher genomic proportion of NS was observed in YRI (~10%) than in CEU (~2.5%) and CHB (~1.9%). One possible reason is that ancient signals of coalescent compression were eliminated by bottlenecks in nonAfrican populations"... which is at odds with AD being more frequent among the supposedly "youngest" population: American Natives.

They also look into Positive Selection (PS) and conclude: "The enrichment of PS signals in brain function beyond 55kya supports the notion that human brain has experienced rapid evolution before OOA. Surprisingly, the 5 ancient brain signals specific to AMH all seem to play important roles in AD pathogenesis. In fact, AD remains arguably a disease unique to humans, as full pathological evidence of AD, particularly AD-related neurodegeneration, are lacking in great apes29. Emerging evidence indicates that AD vulnerability is strongly associated with hyperconnectivity, augmented synaptic and metabolic activities, as well as functional plasticity30. We speculate that the gain of brain function during AMH emergence might have mainly affected synapse networking and neuroplasticity, and this gain was not without a price: it might have led to an increase in structural instability and regional metabolic burden that resulted in a higher risk for neurodegeneration in the aging brain. For the more recent history, the sudden increase of PS signals in stress response in YRI seems to strongly coincide with the emergence of agriculture..."

Once again, PS shaped our brains but also aided development of AD, and again PS is higher among Africans. But they don't have the highest ratios of AD.

I am not quite sure what to make of this. But clearly Africans have the lowest frequency of AD and Latin Americans have the highest. Why? Did a bottleneck make the Amerindians concentrate all the "bad" genes? Is there some external factor that triggers the disease? Does admixture of Amerindians and European settlers increase the risk of AD? It would be interesting to get some data on other groups: Papuans for instance.

Here we have a factor that sets Latinos apart from the rest of the world.

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