Jlhughette wrote:This study is confusing to me. My sister, grandmother and great grandmother all died from AD with ApoE2/4. My mother had AD with ApoE 3/4 and had AD as well. You could say it was because of their lifestyles and diets, which could be true with my grandmother and great grandmother, meat and potato and dessert eaters, but not my sister, a practicing naturopath and acupuncturist, very sick with AD now who still eats a stellar diet mostly organic veg with small amounts of fish and supplement regime. Is the study replacing one of the 4s with a 2? Is it the same as having ApoE2/4 from birth or does silencing just one 4 make more of an impact?
Hi again jlhughette,
Please accept my deep sympathy for the recent death of your father, mentioned in another post. He went way past the average lifespan for a man born about the start of the Depression, and sounds like he raised wonderful kids. You've mentioned earlier that both he and your sister tested as ApoE 2/4 and people in his family all died earlier of heart disease or diabetes. That sounds like the ApoE 2 gene that he passed down to your sister had an outsize effect in previous generations in his family, given the association of ApoE 2 and risk of diabetes, which can then cause heart disease. So you sister presumably inherited her ApoE2 from him and her ApoE 4 from your mother.
Since you have ApoE 3/4, and your dad could only pass on ApoE 2 or ApoE 4, I have to assume you inherited ApoE 4 from him and a "neutral" copy of ApoE 3 from your mom. That would seem to mean that your dad was ApoE 2/4 and your mom was ApoE 3/4. It may be that the early changes you saw in her 40's and 50's were more from Lewy body dementia, since that is most commonly diagnosed in people over the age of 50, according to the Lewby Body Association. https://www.lbda.org/about-lbd/
If I'm interpreting this correctly, the incidence of Alzheimer's which you mentioned earlier occurred in the 80's in your mother and her mother and grandmother, was likely to due to late-life Alzheimer's from that one copy of ApOE 4, along with likely vascular issues, which are the norm, not the exception, in people who are diagnosed in their 80's. Especially among women your mother's generations and older, no one worried about blood pressure in the 120-160 range, and no one referred women to cardiologists, and much of what happens to blood vessels in aging brains may not be visible except in things like hearing loss or changes in vision.
As for the fascinating study in NYC, it's still at the very early stages of looking at safety of three different doses by studying adverse events and maximum tolerated doses. And of course they hope to show that this therapy changes ApoE 4 to ApoE 2. It wouldn't likely be as effective as having ApoE 2/4 from birth, because initially they would only try this on people who had already experienced confirmed amyloid plaques and tau tangles due to Alzheimer's pathology. Having ApoE 2 since birth is usually (but not always, as your sister's fate shows) linked to resistance to developing Alzheimer's pathology.
Only if this study proves there is a safe dose and the drug hits its target will they move to a larger study to see if it also slows or reverses the cognitive and behavioral of people with AD. Here's an excerpt from Clinical Trials.gov:
The [NCT03634007] study will establish a maximum tolerable dose and generate preliminary evidence regarding whether direct administration of AAVrh.10hAPOE2 to the CNS of those Alzheimer's patients will lead to conversion of the APOE protein isoforms in the CSF of APOE4 homozygotes from APOE4 to APOE2-APOE4.
. Gene Therapy for APOE4 Homozygote of Alzheimer's Disease
Your support for your sister is a great gift to her; one I'm sure she appreciates each day.