Keep us posted. I'm still wrapping my brain around the ideal relative distance for this. I see your point about how a rare variant from further back verified through more distant cousin(s), where both branches have dementia is a target. At the same time, to be clear, you'll need to rule out other explanations for both families having common dementia too? I'm thinking this could make a great case study, the more people in both families that can be tested at all genetic distances for high resolution family gene mapping. For example what if your loved one's and her mother's AD is caused by synergy between a pair of genes, that didn't get passed down the sibling or cousin lines? It's my guess that looking at the genetic files of as many close and
distant relatives as possible the better?
Can you try emailing with the researchers studying the south american family with high rates of early onset AD, or the ones studying the US family with high rates of late onset AD (I think mostly in the SE).
Is your new cousin willing to test more family members to help? Is s/he aware of any e4s yet in his or her family?
Have you also transferred your loved one's files to FTDNA to compare against their database too, and GedMatch (free third party)?
No surprise you're not getting many responses on such a loaded issue: serious family illness, privacy concerns, and simply having no interest. Hopefully you share the genealogical interest. It can be best to initially establish trust in the context of family history research and later ask about health. I've done this with some cousin matches myself.
Since, when looking for a rare variant, you'll also want to try to rule out more common causes of the family dementia, you and your 'new' cousin can try to obtain death certificates for key people on the family tree whose health you don't know, constructing a medical family tree. These might show 1) if they had dementia, and 2) if there's a pattern of disease(s) strongly associated with e4. Death certificates aren't always accurate as to cause of death but may wave a flag at you. In my grandmother's case, not sooooo long ago, the dx was atherosclerosis, but in hindsight it was clearly AD. I also found confirmation of my mother's account that her maternal grandfather died of something related to his gall bladder. Gall stone disease
has been associated with e4 among men, so I feel somewhat sure the 4 came from him. By photos he also appears to have the inflammatory/rheumatic/EDS type phenotype that my mother and I have. However, I've not confirmed my mother is where my 4 came from. Just makes the most sense.
Look forward to hearing how this evolves. Hope it's revealing.
ApoE 3/4 > Thanks in advance for any responses made to my posts.