This indicates that assessing the sensitivity of results of GWAS (or GWAS secondary analyses, especially those based on genome-wide statistics) on clinically-diagnosed cases will become increasingly important as the proportion of proxy and biobank cases included in the GWAS increases.
In this preprint, the main consortia working on Alzheimer GWAS combined their efforts to validate an detect new loci associated with AD risk.
We observed 91 genome-wide significant signals (16 nove) . Among these 91 loci, 56 of them are specifically detected in clinically diagnosed AD cases.
๐จJoin our next @DEMONNetworkUK #Genetics and #Omics meeting on THURSDAY 11th September at 2.30 PM (UK Time). Delighted to have @jclambert.bsky.socialโฌ as invited speaker โ โFrom #GWAS to polygenic risk scores in #Alzheimer's diseaseโ
Join the network or DM for more info
In this preprint led by Devrim Kilinc and Pierre Dourlen, we observed that differential expression of BIN1 isoforms in the presynaptic part leads to differential synaptotoxicity. BIN1 isoforms could contribute to the synaptic loss observed in Alzheimer's disease.
www.biorxiv.org/content/10.1...
In this preprint, primarily conducted by Dolores Siedlecki, we established a neuron-microglia co-culture model within the synaptic chamber of a microfluidic device. This compartmented approach enables us to study synapse phagocytosis in close proximity to microglia.
www.biorxiv.org/content/10.1...
Perhaps ๐
I am sure that this controversy over APOE4 did not last long. However, it's true that he insisted, despite the odds being stacked against him, that it was TOMM40, not APOE, that was ultimately responsible for the APOE locus signal.
Why do you say that the research community was sceptical? In fact, it was one of the least controversial genetic results obtained through a gene candidate approach. It was very quickly accepted by the research community because it was systematically replicated.
Today, our article "The entities enabling scientific fraud at scale are large, resilient, and growing rapidly" is finally published in PNAS. I hope that it proves to be a wake-up-call for the whole scientific community.
reeserichardson.blog/2025/08/04/a...
In this new EADB preprint led by Ole Andreassen, we present an improved polygenic hazard score model for AD that demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models.
www.medrxiv.org/content/10.1...
Happy cat on my belly
A new EADB paper published in Nature Communications and led by Kristel Van Steen, Cornelia Van Duijn and Valentina Escott-Price.
We report that machine learning methods have the potential to uncover novel loci that remain undetected by traditional GWAS in Alzheimer.
www.nature.com/articles/s41...
Cette universitรฉ est trop occupรฉe ร sauver la Science en accueillant des chercheurs amรฉricains
FromFB: ๐
5. The PGS/PRS associations mainly capture genetic information related to AD because they weakened as the diagnosis was broadened. The quality of the clinical diagnosis can interfere with the measurement of the association between the PGS/PRS and the AD risk in a given population.
4. However, this is not the case when the PRS includes the APOE region. This indicates that the APOE region appears to contain additional multi-ancestry genetic variability.
3. In contrast to other multifactorial diseases, a cross-ancestry polygenic risk score (PRS) did not systematically outperform the simple PGS when the APOE locus was excluded. A high proportion of AD genetic risk could be already accounted for by the European-ancestry GWAS-defined loci.
2. This simple PGS appears to be enough to detect an AD genetic risk in most ancestry populations, suggesting that most of the various ancestry populations are likely to be affected by shared pathophysiological processes that are driven in part by genetic risk factors.
Our work produced several important findings:
1. The associations between a simple polygenic score (PGS) based on the European GWAS-defined loci and AD risk in European populations is slightly influenced by the APOE genotype, suggesting existence of independent genetic entities for sporadic AD
This work would not have been possible without this global and strongly collaborative effort (particularly Richard Sherva and Mark Logue of the Million Veteran Programme in the US, and Yoontae Kim and Jungsoo Gim of the GARD study in South Korea).
Finally out in Nature genetics !
A long journey to have this paper published. Led by my team, under the EADB umbrella (eadb.eu), the project involved numerous partners worldwide in assessing the genetic complexity of Alzheimer in populations of diverse ancestries.
www.nature.com/articles/s41...
Trumpโs cuts to more than 1700 #NIH grants get court hearing www.science.org/content/arti... by @sarareardon.bsky.social @science.org
#Alzheimers #dementia #neuroscience #science
This is a cumulative maximum intensity projection movie of the endoplasmic reticulum labeled with the membrane marker mEmerald-Sec61B.
Announcing an official fundraising campaign to support my labโs research on APOE4 and Alzheimerโs disease: joinus.cuimc.columbia.edu/participant/.... This campaign is itself an experiment of sorts. But mostly, it's an attempt to save my lab during an unprecedented time of turmoil in academia. 1/9
Here is a direct link to the open access article โช@amit-das.bsky.socialโฌ mentions. alz-journals.onlinelibrary.wiley.com/doi/10.1002/... Tempting to say it feels like a miracle, but this progress always comes down to dedicated study participants, brilliant scientists, and reliably funded science.
A grey heron stalking the waters for fish. Beak is low to the surface of the water. The heron has also sighted a fish and moves slowly not to disturb the water.
I went in search of cygnets. Still not hatched so had to make do with a heron fishing instead. Look at those feet!
#UKWildlife #UKbirding #Birds #Photography #Nature #GreyHeron #photographersunited #PhotographersofBluesky #Sonyalpha
Currently visiting the Medieval Museum in Barcelona. This was painted in 1210โฆ
Je lโai lu tout ร lโheure.
Sans concession et loin des messages en creux adressรฉs aux initiรฉs dans ce gรจne de rapport. Et clairement indiquรฉ lโactivitรฉ nรฉfaste de lโIHU durant le Covid
In this report, to improve our understanding of the genetic architecture of AD in the context of its main genetic driver, the EADB consortium and collaborators performed the largest global genome-wide association studies stratified by ฮต4 and ฮต2 carrier status.
www.medrxiv.org/content/10.1...
And definitively accepted after more than a month of editing to meet all the publisher's requirements.
'BIN1 and Alzheimerโs disease: the tau connection'
by Pierre Dourlen, Devrim Kilinc, Isabelle Landrieu, Julien Chapuis & Jean-Charles Lambert @jclambert.bsky.social
www.cell.com/trends/neuro...
