The suggestion is also probably moot:
zenodo.org/records/1849...
06.02.2026 12:55
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#endalz #medsky #episky
Clarifying the scope of gene editing for Alzheimer's disease prevention
In response to "Heritable polygenic editing: the next frontier in genomic medicine?" by Visscher et al in Nature last year.
zenodo.org/records/1849...
Excited for this one!
2) Approx lifetime risks of AD by 85 years for:
e2/e2: perhaps ~2% (clearly well under 5%)
e3/e3: ~10%
e4/e4: ~60%
You think these are "modest shifts in probabilities"?
1) We've never said "gene edit 95% of the population"
Our data speak to scope for intervening on APOE, not nature of intervention or implementation of such
When high risk is diffuse in pops, interventions may need to be broad academic.oup.com/ije/article/...
But OFC we can consider screening etc
Stressing to public the overlapping roles of both environment and genes is fine...it is naive scientific responses like the one pictured (cited by the Mail) we took issue with. Taking away risk broadly will remove disease (at population level). Tho we could consider gene therapy over magic to do so
...and the coverage from @dailymail.co.uk
www.dailymail.co.uk/health/artic...
My fave commentary on our paper in the Mail last week
Interested to know what @alucassen.bsky.social uses as a definition of causation though!
Here's mine: ajph.aphapublications.org/doi/full/10....
Further reading WRT the topic: zenodo.org/records/1796...
...latest e.g. of this mistake among expert reaction to our paper out last week from @smclondon.bsky.social
Tho not sure if the academic mistook e4 carriage in populations (~25-30%) with AF (~15%) or a typical fraction of AD cases with e4/e4 (~12%)
Courtesy redact
FYI @simonwheeler.bsky.social
Slightly diminish a game.
Metal gear flaccid
Well done to our colleague @dylwil.bsky.social
... more thanks to @alzheimersresearchuk.org, MRC / @ukri.org + others for funding
... Study participants of @ukbiobank.bsky.social, @finngen.bsky.social, A4 study and ADGC
And to journalists for interest & great media coverage, copied below....
Out now!!
www.nature.com/articles/s44...
Intro to this paper pictured below
Huge thanks to collaborators @neilmdavies.bsky.social, @emmylooroll.bsky.social at @uclbrainscience.bsky.social & Sami Heikkinen and Mikko Hiltunen at @uniuef.bsky.social ...
#endalz #episky #medsky
...
...Harking back to the overweight example, this would be like asking how much diabetes occurs in obese ppl, relative to individuals who are overweight and normal weight. Again, there is no special difference in the case of APOE simply because we are talking about genetic risk!
...which introduces two big problems. i) These will underestimate the impact of e4 alone, because they lumped some people with intermediate risk of AD in the reference group alongside the low-risk folk. ii) They don't account for the contributions of intermediate-risk alleles to AD burden at all...
...we can find plenty in large modern cohorts. But historically, e3/e3 was chosen as the most common and allegedly neutral genotype, misleading most PAF estimates. They've almost always estimated the proportion of AD attributable to e4 alone (relative either to e3/e3 or e4 non-carriers)...
...Given the rarity of perhaps the most pronounced protective forms of APOE (Christchurch, Jacksonville and perhaps alleles conferring loss-of-function), such a group is most likely to be e2 homozygotes, who are uncommon but not exceedingly rare (about 1 in 200 ppl in European populations)...
