Kariem Ezzat
@kariemezzat.bsky.social
Research Scientist, Karolinska Institute Co-Founder & CEO, Neuropep Therapeutics #AfricanScientist https://pubmed.ncbi.nlm.nih.gov/?term=Kariem+Ezzat&sort=date https://theprecipitate.blogspot.com/
1 idea, 500 failures lnkd.in/p/d5AkYdhc
The highest clinical trial failure rate for any disease in modern medicine: How both amyloid- and non-amyloid-targeting therapies failed to alter disease course in Alzheimer's disease | Kariem Ezz...
"The highest clinical trial failure rate for any disease in modern medicine" https://lnkd.in/d7cJEmXc More than 500 failed Alzheimer's trials based on one assumption: Neurons produce a toxic peptide ...
lnkd.in
You don't need any aggregated forms to get symptoms if you lose the functional protein, and you can survive aggregated forms if you have enough of the functional protein. For how long the field will ignore this? www.linkedin.com/posts/kariem...
Treatment attempts of neurodegenerative diseases are mostly based on a theoretical house of cards. Only better, more robust physical theories can help. www.linkedin.com/posts/kariem...
A short Swedish saga of bias in Alzheimer's research www.linkedin.com/posts/kariem...
Just to highlight how difficult it is for some eminent researchers in the field to acknowledge that Aβ42 is low in mutation carriers even in absence of plaques, I had this encounter with Science and… ...
Just to highlight how difficult it is for some eminent researchers in the field to acknowledge that Aβ42 is low in mutation carriers even in absence of plaques, I had this encounter with Science and t...
linkedin.com
I didn't know that the recorder could sound so beautiful! A blessing to have found this artist youtu.be/h_DCFf9jXyU?...
Vivaldi: Flautino Concerto In C, RV 443 - Arr. in G Major for Recorder - 1. Allegro
YouTube video by Lucie Horsch - Topic
youtu.be
A good step to finally see this figure in the correct form in a high profile publication. But not enough: www.linkedin.com/posts/kariem...
The error of reification, the fantasy of emergence, the poverty of historicism, and the savior complex #AI #AGI open.substack.com/pub/kariemez...
The Racist Myth at The Core of The AI Hype
It is almost impossible to avoid AI hyped claims whenever you go online or try to watch the news.
open.substack.com
Grateful to Matt for hosting me on his podcast. We discuss the problems with the prion hypothesis & gain of toxic function models of neurodegenerative diseases. www.youtube.com/watch?v=REln... Some of the discussed work can be found here: pubs.acs.org/doi/10.1021/... academic.oup.com/brain/articl...
Overturning a Nobel Prize: New Discoveries in Prion Diseases - Saving Sapiens S3E2
YouTube video by Saving Sapiens Podcast - Hosted by Dr. Matt David
youtube.com
This figure, which is the most famous in Alzheimer's disease (AD) research, is misleading. The 1st & most consistent biochemical abnormality in AD is CSF Aβ42 going down, not up. Ignoring the neuropeptidergic roles of soluble monomeric Aβ42 & their loss due to its depletion.. 1/2
Amazing performance by Ava Bahari, Andreas Brantelid, and the Gothenburg Symphony Orchestra youtube.com/watch?v=zTWD...
Brahms: Double Concerto (Conductor Pekka Kuusisto)
YouTube video by Göteborgs Symfoniker
youtube.com
On the cognitive dissonance between data and theory in neurodegenerative research www.linkedin.com/posts/kariem...
Two recent papers highlight the level of cognitive dissonance in neurodegenerative research, where data clearly contradicting the prevailing hypotheses is still somehow viewed as supporting them… | Ka...
Two recent papers highlight the level of cognitive dissonance in neurodegenerative research, where data clearly contradicting the prevailing hypotheses is still somehow viewed as supporting them. One...
linkedin.com
More people are surviving cancer than ever before, as the 5-year survival rate across cancer reached 70%, according to the American Cancer Society’s new report. www.statnews.com/2026/01/13/w...
More people are surviving cancer than ever before, according to new report
More people are surviving cancer than ever before, as the 5-year survival rate across cancer reached 70%, according to the American Cancer Society’s new report.
statnews.com
A great gift for the holidays from the queen of classical guitar youtu.be/lL9Mabl1Hzo?...
ANA VIDOVIC - 2025 Classical Guitar Concert | Siccas Guitars | BACH, Piazzolla, Schubert
YouTube video by SiccasGuitars
youtu.be
Can prions carry biological information? The answer is definitely NO, not in a million years. We explain why in this recently published paper: pubs.acs.org/doi/10.1021/... Information is actually lost during amyloid formation (pic). More discussion here: www.linkedin.com/feed/update/...
Can Prions Carry Biological Information?
The discovery of the structure of DNA and the elucidation of the molecular mechanisms of replication, transcription, and translation are the foundations of modern biology and medicine. However, in the...
pubs.acs.org
This is our best case yet for the evidence of Aβ42 loss of function in Alzheimer's disease (AD). A neuropeptide is a neuropeptide. Ignoring its functions and the fact of its universal depletion in AD and other dementias is a choice made by the field not a scientific mystery. 1/2
Alberto Espay@albertoespay.bsky.social · 12mo agoFor decades, we have tried to suppress γ-secretase, lower Aβ42 levels, or remove amyloid from the brain. We show that PSEN1 mutations already reduce γ-secretase activity and lower Aβ42. Why restoring Aβ42 is the way forward for #Alzheimers, via @Brain1878 academic.oup.com/brain/articl...
What is the physical basis of "catching a cold"? We attempted to answer this question in this preprint. It has something to do with one of my favorite concepts, phase transition, this time temperature-dependent and not concentration/nucleation dependent. www.linkedin.com/posts/kariem...
Lipid Composition Controls Temperature-Dependent Viral Immune Response in Human Bronchoalveolar Space | Kariem Ezzat
"Dress well so you don't catch a cold!" is a perennial advice every parent has given their child at some point. In 2020, just before the coronavirus pandemic hit, we were trying to understand what is ...
linkedin.com
Nice and clear evidence of the synaptogenic properties of Aβ peptides at physiological concentrations from the Südhof lab pubmed.ncbi.nlm.nih.gov/41026542/
Aggregation shifts amyloid-β peptides from synaptogenic to synaptotoxic - PubMed
Whether amyloid-β (Aβ) peptides are synaptogenic or synaptotoxic remains a pivotal open question in Alzheimer's disease research. Here, we chronically treated human neurons with precisely controlled c...
pubmed.ncbi.nlm.nih.gov
"Trial investigators also observed a reduction in the level of a toxic protein linked to neurodegeneration in the spinal fluid of people who received the therapy." Not true, investigators reported earlier a 40% increase of mHTT in the CSF. (pic. from uniqure.gcs-web.com/news-release...) 1/2
Nature@nature.com · last yr.A one-time gene therapy can markedly slow the progression of Huntington’s disease, potentially paving the way for the first ever treatment to alter the course of this rare, inherited brain disorder. go.nature.com/4nu6YMs
About Uniqure's great Huntington's results: www.linkedin.com/posts/kariem...
Great news today from Uniqure's Huntington's gene therapy, which showed 75% disease slowing. It is intriguing, however, that similar to lecanemab in Alzheimer's disease, the only drugs tha...
Great news today from Uniqure's Huntington's gene therapy, which showed 75% disease slowing. It is intriguing, however, that similar to lecanemab in Alzheimer's disease, the only drugs that work in ne...
linkedin.com
An amazing and thrilling story of how scientific inquiry and drug development done correctly can lead to medical wonders www.statnews.com/2025/06/23/f...
The decades-long journey to Gilead’s twice-a-year HIV prevention drug lenacapavir
Gilead’s twice-a-year HIV prevention drug lenacapavir is 30 years in the making. Here’s the story behind it.
statnews.com
Due to the fragile nature of our existence & the complexity of our environment, we're equally vulnerable. Vulnerability is the true basis of equality, as explained in this foundational paper by @mlafineman.bsky.social. More important to highlight now than ever. openyls.law.yale.edu/handle/20.50...
The Vulnerable Subject: Anchoring Equality in the Human Condition
openyls.law.yale.edu
α1-Antitrypsin (A1AT) deficiency is a great example of loss-of-function pathogenesis due to protein aggregation. Aggregates in liver -->⬇️A1AT in plasma --> protein replacement as treatment. Same mechanism for amylin in diabetes: Aggregates in pancreas-->..1/3 www.nature.com/articles/nrd...
When the theory is stronger than experiment. The authors struggling to interpret clearly +ve effects of soluble Aβ42 (enhanced differentiation & myelination) as -ve (precocious differentiation & dysregulated myelination!), because it has to be bad, right? 1/2 onlinelibrary.wiley.com/doi/10.1002/...
Amyloid‐β Dysregulates Oligodendroglial Lineage Cell Dynamics and Myelination via PKC in the Zebrafish Spinal Cord
Amyloid-β peptide induces early oligodendrocyte differentiation and dorsal myelination in the zebrafish larvae spinal cord. Pan-PKC inhibitor Gö6983 restores the aforementioned alterations in oligode....
onlinelibrary.wiley.com
Seeding can also lead to loss of function www.cell.com/neuron/fullt...
Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures
TDP-43 pathology characterizes neurodegenerative diseases. Scialò et al. use in vitro-generated and patient-derived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic aggregation ...
cell.com
Happy that this message is finally getting across, that protein overexpression can also lead to loss of function in neurodegenerative amyloid pathologies www.nature.com/articles/s41...
Happy to see more papers addressing loss of function as a potential pathogenic mechanism in neurodegenerative diseases febs.onlinelibrary.wiley.com/doi/full/10.... www.nature.com/articles/s41...
FEBS Press
Neurodegeneration is thought to arise due to the disruption of the protein homeostasis. In synucleinopathies, alterations in the levels of functional and aggregated aSyn lead to proteinopenia and pro...
febs.onlinelibrary.wiley.com
A good illustration of how new detection technologies are finding direct evidence of viral involvement in neurodegenerative diseases, something that was difficult before & led to the premature exclusion of viruses from disease etiology & the birth of the prion hyp. 1/3 www.cell.com/cell-reports...
Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease
Hyde et al. found elevated HSV-1 protein expression in Alzheimer’s disease, with phosphorylated tau strongly colocalizing with HSV-1 proteins. They demonstrated that tau phosphorylation responds to HS...
cell.com
