new here- progranulin defect, not APOE4

[progranulindefect]

I too found out about a genetic dementia risk through 23andme. the risk is for an early onset dementia called frontotemporal lobe dementia (ftd for short). this kind of dementia was not highlighted in the 23andme health report (back when they gave out health reports before the fda shut that down). how i found out about my risk was through using snpedia and promethease. i found out i have the progranulin defect, which has been associated with ftd. my husband also has the defect (we both have one risk allele), and one daughter has two risk alleles, which is associated with another pathology. i am hoping i have some protective genes in the mix since my paternal aunt didn't get her dementia until she was in her 70's/80's, and my father/grandfather seem not to have dementia. my mother had some symptoms, but there were mild- what killed her was metastatic breast cancer at 78.

so since 23andme did not hightlight ftd in its reporting, there is no group of individuals who were discussing their genetic vulnerability to ftd- so you guys lucked out in that way. i would prefer to have something specific to the progranulin defect, but nothing exists, and the care-giver forum i am on has no subset of people with the progranulin defect on it. those people are just barely keeping their heads above water. hopefully this forum has an area where people discuss ways to relieve caregiver burden on a large scale, and ways to ease the suffering of people with dementia throughout the disease span, including discussion about the farce that is long term care insurance.

anyway, one thing i haven't been able to find is people with a dementia risk doing self-experiments which are a little more rigorous. for example, planning one intervention and doing some kind of pre/post testing. i am planning on doing this myself with blood sugar/sleep/exercise (since both my parents are/were diabetic, i will have high bg levels eating food that won't affect others in that way). i want to test my ability to remember number sequences backwards- things like that.

has anyone else here done similar self-testing to tease out which interventions have most bang for the buck? i'm going to do focus on improvement in bg levels/sleep/exercise first because these are factors which already have overwhelming evidence associated with them. I want to see how much i improve cognitively after i really focus on them. later i will add in other interventions.

[Julie G]

Welcome Pro! Is this the post you thought was lost? Just delayed due to moderation- sorry. You've got my attention. FTD runs in my family. Do you recall the snips to identify this defect?

[Julie G]

anyway, one thing i haven't been able to find is people with a dementia risk doing self-experiments which are a little more rigorous. for example, planning one intervention and doing some kind of pre/post testing. i am planning on doing this myself with blood sugar/sleep/exercise (since both my parents are/were diabetic, i will have high bg levels eating food that won't affect others in that way). i want to test my ability to remember number sequences backwards- things like that.

has anyone else here done similar self-testing to tease out which interventions have most bang for the buck? i'm going to do focus on improvement in bg levels/sleep/exercise first because these are factors which already have overwhelming evidence associated with them. I want to see how much i improve cognitively after i really focus on them. later i will add in other interventions.

Pro, our site is full of N=1 experiments that our members have shared with pre & post testing, mainly of biomarkers correlated with improved cognition as opposed to the actual cognitive testing itself. You're proposing actually checking to see if improved blood glucose levels have an impact on your cognition? Interesting. Wouldn't something like Luminosity or BrainHQ be helpful for that purpose?

[progranulindefect]

"...A functional effect is suggested in many studies such as "GRN variant rs5848 reduces plasma and brain levels of granulin in Alzheimer's disease patients" [PMID 22890097] and "Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer's disease" [PMID 19625741OA-icon.png]. In addition "rs5848 polymorphism and serum progranulin level" [PMID 21047645OA-icon.png] showed that progranulin level is affected by number of (T) alleles..."

go to snpedia and put rs5848 into the search field. all sorts of info pops up. then on the right hand side are all the genetic testing companies. i click on 23andme and get my results that way. remember that when it comes to alleles, C=G and A=T, i believe. i also have some snp that makes it easier for viruses like herpes to slip passed the blood/brain barrier. i will check out those sites (luminosity and brainhq). i will also add some of my own tests, like writing as neatly as i can with a mouse, typing, and digit recitation. it would be better if i had a smart phone to record stuff like sleep history, but i will get one in september.

juliegee, who in your family has ftd? are you familiar with the ftdsupportforum? those people are superheroes over there, no joke.

[progranulindefect]

https://www.snpedia.com/index.php/Front ... l_dementia

the above link has more info on ftd.
i have only investigated progranulin as that's what came up in promethease. there are other snps associated with various forms of ftd. i've also heard that running your raw genetic data through promethease every 6 months is reasonable as new studies are always being added to it, and you'll get the most up to date info.

i also wonder how accurate the results are for 23andme. they do seem to match up with other known problems we have in the family. has anyone here gone to several genetic testing companies to verify results from one testing company?

[ApropoE4]

FTD isn't a very common condition, and even if the increased risk reported in some studies holds, the odds of developing it still seem to be far below 1% (and the odds for the specific subtype the variant promotes are far lower yet).

The best course of action therefore seems to be not worrying about it (although of course there may be other causes of familial dementia that are interesting to explore)

[J11]

It is very important not to be overly enthusiastic about much of the genetic results that occurred before the era of truly large scale GWAS
that occurred prior to about 2014.

Alzforum has been working through a rethink of much of the results from that time.
It will be very interesting to see how many of the 695 listed Alzheimer's genes will make the cut after
they relaunch Alzgene. Probably not that many.

The IGAP GWAS has essentially proven without any doubt that there are no remaining common SNPs that significantly increase AD risk to be found. There might not even be any remaining common SNPs that increase risk by even 10%!

APOE epsilon 4 is fairly unique in genetics. There have not been that many common disease causing variants found in the entire human
genome. Why would there be? Whatever happened to evolution?

The listing on Alzforum for rs5848 includes only a few hundred AD and controls for the different genotypes and does not
look especially convincing. The difference in heterozygotes is only 1.4%; the 95% confidence interval
almost includes 1. In the IGAP study with nearly 100,000 people the GRN gene was not reported.

http://www.alzgene.org/meta.asp?geneid=584&polyID=2137

[Julie G]

Pro, It's interesting to learn more about FTD. Thanks for sharing that information. I'll have to track down my snips. From what you've uncovered, are the strategies different for preventing FTD than LOAD?

My paternal Uncle is the affected family member. As my father died when I was very young, I'm particularly interested in both of his brother's neurological health. One is 3/4 and had Parkinson's. (He died recently.) I don't know the other's APOE genotype, but he is the one with FTD.

[Stavia]

Pro I haven't said hi and welcome yet. Welcome!
Some responses:
1. Yes many of us test and tweak.
2. I haven't rechecked my 23andme for accuracy.
3. I agree with Julie that current strategies we employ might be of benefit to you.
4. I understand how scary even a smaller chance of a nasty gene is.
5. My head is full with apoe4 so I'm sorry I have nothing to add about FTD.

[progranulindefect]

juliegee asked:
"From what you've uncovered, are the strategies different for preventing FTD than LOAD?"

julie, that's the problem- I have found no prevention strategies for people with the progranulin defect. no one with the various genetic vulnerabilities to ftd have organized to put out info, and i have found no scientific studies that specifically address ftd and prevention.


This email has just reduced my anxiety a lot:

"I apologize for my late response. The defect at SNP rs5848 that you refer to is seen in approximately 20% of the population (1 in every 5 individuals), so while it may be lowering progranulin levels somewhat it is by no means causing FTD."

It is from a scientist working on the link between the progranulin defect and ftd. I think at worst what I have is a vulnerability to ftd and other disorders associated with lower progranulin levels, but it is not inevitable like I was worried about. Scientists are still trying to unravel what has to also be present in addition to genetic defects like mine. As far as I know, they are still just doing this very basic science. Meanwhile, I still have some cognitive decline, and will work on that no matter what the ultimate cause. I appreciate everyone's support