New Study Indicates Genes Don't Always Dictate Alzheimer's

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deborahk
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New Study Indicates Genes Don't Always Dictate Alzheimer's

Post by deborahk »

This is an interesting study of identical triplets and suggests developing Alzheimer's is not exclusively linked to our genes.

https://www.beingpatient.com/alzheimers ... -triplets/
NF52
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Re: New Study Indicates Genes Don't Always Dictate Alzheimer's

Post by NF52 »

deborahk wrote:This is an interesting study of identical triplets and suggests developing Alzheimer's is not exclusively linked to our genes.
https://www.beingpatient.com/alzheimers ... -triplets/
Thanks for sharing this, Deborah!
The source article is available in entirety here: Genetic and epigenetic study of an Alzheimer’s disease family with monozygotic triplets https://academic.oup.com/brain/article/ ... 75/5580538

A few interesting notes: The triplets, and the offspring of one triplet who developed Early-Onset Alzheime'rs Disease (EAOD) have one copy of ApoE 4, and other genes which have been associated with risk for EAOD. The offspring of the one sibling who developed Early-Onset AD at age 50 appears to have been affected by one of the risk genes. The mother of the triplets lived to 97, and died of Parkinson's disease with dementia, so presumably some factors are supporting longevity. The triplet who has no cognitive complaints or issues in daily living skills, does score a 22/30 on the Mini-Mental Status Exam and scores similar to a sibling within the "impaired" range on a test called TOR-CA. It seems likely that in the U.S., that would be considered equivalent to a diagnosis of Mild Cognitive Impairment (a profile I would still call a victory at age 85!)

Here's an excerpt from the Abstract and Conclusion (emphasis added):
Age at onset of Alzheimer’s disease is highly variable, and its modifiers (genetic or environmental) could act through epigenetic changes...DNA methylation is also linked to ageing—the strongest Alzheimer’s disease risk factor... We conducted a clinical, genetic and epigenetic investigation of a unique Ashkenazi Jewish family with monozygotic triplets, two of whom developed Alzheimer’s disease at ages 73 and 76, while the third at age 85 has no cognitive complaints or deficits in daily activities. One of their offspring developed Alzheimer’s disease at age 50. Targeted sequencing of 80 genes associated with neurodegeneration revealed that the triplets and the affected offspring are heterozygous carriers of the risk APOE ε4 allele, as well as rare substitutions in APP (p.S198P), NOTCH3 (p.H1235L) and SORL1 (p.W1563C). In addition, we catalogued 52 possibly damaging rare variants detected by NeuroX array in affected individuals. Analysis of family members on a genome-wide DNA methylation chip revealed that the DNA methylation age of the triplets was 6–10 years younger than chronological age, while it was 9 years older in the offspring with early-onset Alzheimer’s disease, suggesting accelerated ageing.
So when the 50 year old offspring was diagnosed with EAOD, s/he had a biological DNA methylation age of 60, and his/her parent, who would have been 75 at that time, had a biological age of 65--only 5 years difference in biological aging between parent and child!
4/4 and still an optimist!
Nikki2019
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Re: New Study Indicates Genes Don't Always Dictate Alzheimer's

Post by Nikki2019 »

deborahk wrote:This is an interesting study of identical triplets and suggests developing Alzheimer's is not exclusively linked to our genes.

https://www.beingpatient.com/alzheimers ... -triplets/
This would indicate that all of our effort is worthwhile. :) The article mentions the gene that is thought to repress AD; however, since the three individuals were born with the same genes then all three or none would have this. Now... I was wondering why couldn't they clue us into what differences these three had in their lifestyles? :?:
As E4 s, we are inherent fighters and don't give up so easily.
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