Genes that control dementia in the face of advancing Alzheimer's disease

We know from a variety of studies (and my experience!) that cognitive decline may be suppressed even when Alzheimer's disease advances.  The classic example is the Nun Study, in which a few women were found on autopsy to have evidence of advanced Alzheimer's disease but who did not display evidence of dementia before they died.  What was different about these people?  Inquiring minds want to know.

I came across an interesting study published in the journal Acta Neuropathologica Communications that found genetic makeup can play a role, especially with genes involved in immune response.  Researchers  from the Netherlands studied the brains of a sample of deceased people where it could be determined that they did or did not show evidence of dementia before they died.  Also, it could be determined whether they did or did not have Alzheimer's disease.  The presence of amyloid plaques, certain tau proteins, and atrophy gave evidence of Alzheimer's pathology.  They compared these parameters to the genetic makeup of these people.  The article was entitled, "Gene-expression profiling of individuals resilient to Alzheimer's disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response."  (I'm sure there's a longer title somewhere, but I haven't seen it yet.)

Long story short, there were people in the study with evidence of both Alzheimer's disease and dementia, a much smaller number of people without dementia but with evidence of Alzheimer's disease, and a number of people with evidence of neither Alzheimer's nor dementia.  There were certain special genes "expressed" in the population with Alzheimer's disease who did not have dementia that were not expressed in the other populations.  ("Expressed" means they were activated for use in producing specific proteins.)  These genes were largely associated with the immune response.  There was also correlation with the related proteins to how the brain reacts to metals entering the brain and in the processing of energy.

Note that, in Alzheimer's disease, it's metals in the brain that may oxidize and cause damage, which is why we eat blueberries.  Also, PET scans used to diagnose Alzheimer's disease are looking at how glucose is processed in the brain for energy.  There is a progressive breakdown in the metabolism of glucose in Alzheimer's disease.  So proteins from these genes, either directly or indirectly, appear to be suppressing the way in which Alzheimer's disease is promoting oxidation and interfering with metabolism of glucose.

I am certain that you do not want to read the research report.  However, if you're interested, here's an article from Science Direct that breaks it down for you in a way that's easier to understand.  But the article gets into something dearer to my heart that's not addressed directly in the research paper.  That is the population of people without these special genes and have Alzheimer's disease, but do not have dementia.  Since I was developing dementia, and my MRIs had the biomarkers for Alzheimer's disease, I surmise that I am one of these.  With regard to this population, the authors of the magazine article echo what we said in Beating the Dementia Monster -- lifestyle changes are the key to turning the disease around.