How I found out about my PSEN1 Mutation

Family history was a warning sign.

In some ways I’ve always had this latent, pessemistic fear of Alzheimers and it’s something that has shaped my life to a certain extent. My Nan was diagnosed with vascular dementia at 50 but in hindsight it was likely the arg269his mutation. My father also lived in fear of this until it was diagnosed when he was 66..

My experience of these two cases have been very different. My sweet, wonderful, grandmother gradually got more and more confused but was still capable, moving from her flat to warden monitored living but she ws still able to catch a bus, shop, have a conversation etc until she faded a bit more and went into a care home at around 60. She fell, broke her hip, never walked again and passed away several years later. My final memories of her were of her on a air compresseed mattress blankly looking up at the ceiling.

My Dad , now 70 you can still have a reasonably short conversation with. He’s losing his mobility, the lack of muscle use is making him progressively weaker and his eyesight or at least, the signals from the eyes to the brain, are not very good at all. But considering he’s now four years older than when his mum died and they both had the same genetic variant it stands as a good illustration of the massive variability to this disease.

But it’s not good for someone like me who now has absolutely no idea when this thing is going to come knocking at my door; although it’s not entirely bad.

How I found out my situation in the best worst way possible.

My Dad was going for genetic testing due to his mum’s history. I don’t actually know how often a GP will ask for a genetic test for variants on the common genes but in my personal opinion anyone with Alzheimer’s, even over the age of 65 should be offered it as standard. Medical research has one hand behind their back and can always do with a much bigger dataset.

So while I was waiting for papa bear’s results I sent off for a 23andme basic test. The thing that isn’t commonly known about this service is you can download the raw data as a text file and pop that into an interpreter like Promethease. Promethease will run your genome against a wealth of papers based on genetics and will give you a list of reports based on relevance to your genetic code.

Which is amazing when you think about it. You just have to NOT take everything too seriously. But in my case, a big red flag popped up to say that I carried a mutation on the arg269his gene which was indicative of EOAD. So that wasn’t pleasant but I was looking for this information and got it. So in a way I was prepared for it. The first few weeks I was angry. You see, my family life was normal compared to most but my relationship with my Dad was tentative, often fractuous and after getting away from this, finding someone, settling down and having a home after some struggling ‘Dad’ comes back with one last whammy.

But this isn’t fair – I’m saying the above because you, friend, might be having those feelings towards a parent too, you might have just found out and are in a bad place. I reconciled this with myself fairly quickly. As in, how the hell was he to know at the time when he didn’t know until this year? It wasn’t deliberate, or malicious. It was just bad luck. It was 50/50 and my coin toss just wasn’t in my favour. The difference between him finding out now and my finding out is that my parents are still alive and he feels terrible about it and he’ll never escape that. HIs mum will never know. What other alternative is there? That I was never born at all? That I’d never get to experince the late afternoon sun on my skin. warm duvets on a Sunday and the green and browns of late autumn trees?

I contacted my fathers neurologist and he said that 23andme isn’t a clinically verified test which is true. It also was mentioned on the Promethease report that ‘this variant appears much more than expected in clinivar’ – i.e. it’s so rare it shouldn’t pop up in the results as much as it does…but it does.

Tangent –

‘Generally Early Onset Alzheimer’s’ is defined as anything that appears in those under the age of 65. However, some variants are so variable in their age of onset that my particular variant may be a lot more present in those over the age of 65 and because those over 65 don’t usually get tested I could have a much wider range of onset and it could go some way to explain why my Nan was diagnosed at 50 but my father at 66 – if researchers are only getting results from those in the ranges of 45-65 then the mena age of onset will be within that range’

Following on from this I went with my Dad to the NNRI at Queens square to get his genetic test results. Professor Fox advised my Dad there was a genetic component to his Alzheimer’s and look at me and said ‘it was the same variant that I found via 23andme’.