Jean-Charles Lambert

🚨Join our next @DEMONNetworkUK #Genetics and #Omics meeting on THURSDAY 11th September at 2.30 PM (UK Time). Delighted to have @jclambert.bsky.social‬ as invited speaker – “From #GWAS to polygenic risk scores in #Alzheimer's disease”

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BIN1 expression in the presynaptic compartment leads to isoform-specific synaptotoxicity Alzheimer’s disease (AD) is characterized by a strong genetic predisposition and by an early loss of synaptic connectivity that strongly correlates with cognitive deficit. Some genetic determinants co...

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...

Inflammation-enhanced synapse-specific phagocytosis by adult APP microglia in a microfluidic neuron–microglia co-culture model Microglia play a critical role in synapse remodeling and neuroinflammation, both of which are dysregulated in Alzheimer′s disease (AD). However, most in vitro models rely on neonatal or immortalized m...

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 😉
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.

A do-or-die moment for the scientific enterprise Reflecting on our paper “The entities enabling scientific fraud at scale are large, resilient, and growing rapidly”

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...

Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation Objectives Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer’s disease (AD). In this study, we present an improved PHS model ...

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

Machine learning in Alzheimer’s disease genetics - Nature Communications Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional...

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 université est trop occupée à sauver la Science en accueillant des chercheurs américains

FromFB: 😂

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).

Transferability of European-derived Alzheimer’s disease polygenic risk scores across multiancestry populations - Nature Genetics Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary ...

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...

Trump’s cuts to more than 1700 NIH grants get court hearing District judge could declare terminations unlawful—or toss suit based on technicalities

Trump’s 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 lab’s research on APOE4 and Alzheimer’s 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 ‪@amit-das.bsky.social‬ 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 1210…

Je l’ai lu tout à l’heure.
Sans concession et loin des messages en creux adressés aux initiés dans ce gène de rapport. Et clairement indiqué l’activité néfaste de l’IHU durant le Covid

APOE stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers’s disease Among the more than 90 identified genetic risk loci for late-onset Alzheimer’s disease (AD) and related dementias, the apolipoprotein E gene ( APOE ) ɛ2/ɛ3/ɛ4 polymorphism remains the longstanding ben...

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 ε4 and ε2 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 Alzheimer’s disease: the tau connection'

by Pierre Dourlen, Devrim Kilinc, Isabelle Landrieu, Julien Chapuis & Jean-Charles Lambert @jclambert.bsky.social

www.cell.com/trends/neuro...

BIN1 and Alzheimer’s disease: the tau connection Bridging integrator 1 (BIN1) is a ubiquitously expressed protein that plays a critical role in endocytosis, trafficking and cytoskeletal dynamics. In …

When I was a student, I dreamed of one day publishing in Trends In Neurosciences. So I'm proud that we had the opportunity to write an invited review on BIN1, a major genetic determinant of Alzheimer's disease that we've been working on for over 10 years.

www.sciencedirect.com/science/arti...

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