#amyloid — Public Fediverse posts
Live and recent posts from across the Fediverse tagged #amyloid, aggregated by home.social.
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Bart De Strooper presented at the Copenhagen AD/PD-conference an excellent sketch of the three main inflection points in the pathophysiological evolution of Alzheimer's disease, https://www.alzforum.org/news/conference-coverage/big-picture-three-inflection-points-mark-amyloid-cascade
My own transition from amyloid plagues to p-tau and tangles was retarded by a four years' anti-amyloid therapy in a clinical reaearch project during 2017-22 (aducanumab). Sadly, the most probable explanation for my rapidly worsening cognitive problems may indeed be the tau-tangles, which I somehow avoided earlier. I know there are experimental therapies around somewhere for those gremlins too, but sadly not within my own reach. With respect to my AD, I'm afraid, it's "too late, my friend".
I encourage anybody with a slowly lethal disease to keep mentally in touch with it as long as you can. That's what we human beings were made for. 🤗
#alzheimer #ad #at #disease #medical #amyloid #tau #lethal #sairaus #alzForum #realism #humanity #reflection #thinking #dying #terminallyill #metacognition #tietoisuus #consciousness
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Bart De Strooper presented at the Copenhagen AD/PD-conference an excellent sketch of the three main inflection points in the pathophysiological evolution of Alzheimer's disease, https://www.alzforum.org/news/conference-coverage/big-picture-three-inflection-points-mark-amyloid-cascade
My own transition from amyloid plagues to p-tau and tangles was retarded by a four years' anti-amyloid therapy in a clinical reaearch project during 2017-22 (aducanumab). Sadly, the most probable explanation for my rapidly worsening cognitive problems may indeed be the tau-tangles, which I somehow avoided earlier. I know there are experimental therapies around somewhere for those gremlins too, but sadly not within my own reach. With respect to my AD, I'm afraid, it's "too late, my friend".
I encourage anybody with a slowly lethal disease to keep mentally in touch with it as long as you can. That's what we human beings were made for. 🤗
#alzheimer #ad #at #disease #medical #amyloid #tau #lethal #sairaus #alzForum #realism #humanity #reflection #thinking #dying #terminallyill #metacognition #tietoisuus #consciousness
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Bart De Strooper presented at the Copenhagen AD/PD-conference an excellent sketch of the three main inflection points in the pathophysiological evolution of Alzheimer's disease, https://www.alzforum.org/news/conference-coverage/big-picture-three-inflection-points-mark-amyloid-cascade
My own transition from amyloid plagues to p-tau and tangles was retarded by a four years' anti-amyloid therapy in a clinical reaearch project during 2017-22 (aducanumab). Sadly, the most probable explanation for my rapidly worsening cognitive problems may indeed be the tau-tangles, which I somehow avoided earlier. I know there are experimental therapies around somewhere for those gremlins too, but sadly not within my own reach. With respect to my AD, I'm afraid, it's "too late, my friend".
I encourage anybody with a slowly lethal disease to keep mentally in touch with it as long as you can. That's what we human beings were made for. 🤗
#alzheimer #ad #at #disease #medical #amyloid #tau #lethal #sairaus #alzForum #realism #humanity #reflection #thinking #dying #terminallyill #metacognition #tietoisuus #consciousness
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Bart De Strooper presented at the Copenhagen AD/PD-conference an excellent sketch of the three main inflection points in the pathophysiological evolution of Alzheimer's disease, https://www.alzforum.org/news/conference-coverage/big-picture-three-inflection-points-mark-amyloid-cascade
My own transition from amyloid plagues to p-tau and tangles was retarded by a four years' anti-amyloid therapy in a clinical reaearch project during 2017-22 (aducanumab). Sadly, the most probable explanation for my rapidly worsening cognitive problems may indeed be the tau-tangles, which I somehow avoided earlier. I know there are experimental therapies around somewhere for those gremlins too, but sadly not within my own reach. With respect to my AD, I'm afraid, it's "too late, my friend".
I encourage anybody with a slowly lethal disease to keep mentally in touch with it as long as you can. That's what we human beings were made for. 🤗
#alzheimer #ad #at #disease #medical #amyloid #tau #lethal #sairaus #alzForum #realism #humanity #reflection #thinking #dying #terminallyill #metacognition #tietoisuus #consciousness
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Bart De Strooper presented at the Copenhagen AD/PD-conference an excellent sketch of the three main inflection points in the pathophysiological evolution of Alzheimer's disease, https://www.alzforum.org/news/conference-coverage/big-picture-three-inflection-points-mark-amyloid-cascade
My own transition from amyloid plagues to p-tau and tangles was retarded by a four years' anti-amyloid therapy in a clinical reaearch project during 2017-22 (aducanumab). Sadly, the most probable explanation for my rapidly worsening cognitive problems may indeed be the tau-tangles, which I somehow avoided earlier. I know there are experimental therapies around somewhere for those gremlins too, but sadly not within my own reach. With respect to my AD, I'm afraid, it's "too late, my friend".
I encourage anybody with a slowly lethal disease to keep mentally in touch with it as long as you can. That's what we human beings were made for. 🤗
#alzheimer #ad #at #disease #medical #amyloid #tau #lethal #sairaus #alzForum #realism #humanity #reflection #thinking #dying #terminallyill #metacognition #tietoisuus #consciousness
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I Must admit that I didn‘t know this type of #amyloid existed.
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HAI2026 konferenssin uutisia kootusti, https://www.alzforum.org/news/conference-coverage/human-amyloid-imaging-conference-hai2026
Vastaavasti 2025 lopun CTAD:ista https://www.alzforum.org/news/conference-coverage/clinical-trials-alzheimers-disease-ctad-2025, ja kesän AAIC:ista https://www.alzforum.org/news/conference-coverage/alzheimers-association-international-conference-aaic-2025
#alzheimer #dementia #memory #muisti #tutkimus #research #clinical_trials #news #alzForum #amyloid #sairaus #imaging #tau #medical
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Alzheimer’s steals memories, but knowledge is our best defense!
🧠✨🧠Dive into my latest podcast with the Medical Society of Delaware, with an update on groundbreaking research which is flipping the script on dementia.
Hit play, tag someone who needs this must-hear update and let’s turn awareness into action.
Who in your circle should tune in?
#dementia #alzheimers #amyloid #DementiaDecoded #ShareKnowledge
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Experimenting with #ThT stain on #spider webs to see if it successfully bonds to the beta chain #fibrin / #amyloid like components. I've applied the stain and naturally under 460nm webs fluoresce the expected green. I'm waiting for the sample to completely dry before differentiating with alcohol and then using a water based mount to finally disassociate the unbounded stain from the webs and other artefacts. All being so, we might be left with ThT stained #spidroins #science #biology #microscopy
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SciTech Chronicles. . . . . . . . .Feb 2nd, 2025
#AM #gastrointestinal #mucus #glycan #mucin #Alzheimer’s #amyloid #Talin #Tau #APP #photothermal #polyaniline #polydopamine #durability #thermogalvanic #Iron #scalability #stability #seismometers #uncontrolled #Chinese #SpaceX #damage
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SciTech Chronicles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Jan 12, 2025
#TBI #injury-related #2021 #brain #function #proton #irradiation #molecules #polymers #Linux #OS #Distribution #kernel #Torvalds #security #CLI #Ultrasound #amyloid-β #Alzheimer’s #Plaques #Polar #Vortex #southern #lobe #blocking
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A long-awaited AlzForum's take on the news that ApoE4 homozygotism means in fact an AD pathology (though not necessarily dementia before death), https://www.alzforum.org/news/research-news/do-two-apoe4-alleles-always-mean-alzheimers
The comments-section gives a glimpse of some of the trenchlines regarding the treatment of dementia, but I guess the prevention-camp has only just been strirred up from their Sleeping Beauty's slumber.
I, as an example, still have only a 1 % measured risk of acquiring AD, according to some widely used screens, and no "preventable risk factors" except maybe age. Too bad, my genetic inheritance seems to have been enough to skew the Amyloid-Beta balance early on. Luckily, I was recruited to the aducanumab-study for four years (a precursor of lecanemab with more severe side-effects), and probably got some more years to be able to think things like these.
#alzheimer #research #medical #APOE4 #alzForum #dementia #ad #alzheimers #amyloid #lecanemab #aducanumab #prevention #cure
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Alzheimer’s disease seen in near 100% APOE4 homozygotes
“Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to #APOE3 homozygotes.
By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive #amyloid scans, with the prevalence of these markers increasing with age, indicating near-full penetrance of AD biology in #APOE4 homozygotes”
#Alzheimers #Dementia
https://pbs.twimg.com/media/GM524u1bEAAJoAl.jpg -
What is known as the #prodromal phase, the years when #Alzheimer's is attacking the brain but the clinical presentations may not yet be apparent. "One early hallmark is that sticky protein called beta-amyloid, which over time builds up into brain-clogging #plaques. #Amyloid alone isn’t enough to damage memory — plenty of healthy people’s brains harbor a lot of plaque. An abnormal #tau protein that forms neuron-killing tangles is one of several co-conspirators."
https://www.yahoo.com/news/silent-brain-changes-precede-alzheimers-221628452.html
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"ECSIT binding induces a major conformational change in the FAD-binding loop of ACAD9, releasing the FAD cofactor and converting ACAD9 from a fatty acid β-oxidation (FAO) enzyme to a CI assembly factor. We provide evidence that ECSIT #phosphorylation downregulates its association with ACAD9 and is reduced in #neuronal cells upon exposure to #amyloid-β (Aβ) oligomers."
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@macesari Interesting, to say the least. Fine, if geriatricians educate themselves about the neurological and pharmacological intricacies of AD (which begins maybe two decades before any symptoms), but very many memory patients meet a geriatrician way too late. I haven't met one thus far, and was a guinea-pig in aducanumab-research for 4 years (got it 10 mg/kg). From my own experience and what I have studied during the journey, I concur with the minimal clinical advantage and the heavy burden of monthly infusions. But it is quite another question, who should lead the patience care at MCI-level and before, where MAB's can still make a difference.
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Disease Modifying Therapy for #Alzheimer's #Dementia
"The long-awaited era of disease-modifying therapy for Alzheimer’s disease has finally arrived and will substantially impact how the disease is perceived and managed. The drugs closest to widespread clinical implementation are #lecanemab and #donanemab—intravenous #MonoclonalAntibodies that remove β #amyloid plaques from the #brain and can slow cognitive and functional decline."
#leqembi
https://cnmri.com/2023/07/21/disease-modifying-therapy-for-alzheimers/ -
Unfortunately the CAG repeat GRC coincides with another great meeting: The FASEB Protein Aggregation Conference: Exploring Rugged Landscapes. #amyloid #llps and more! this year in Malahide, Ireland Jun 11-15 https://web.cvent.com/event/720adec4-52f0-4173-ba93-8681b42780eb/summary. #PACSRC
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ATP-Driven Molecular Chaperone Machines
#Molecular #chaperones are proteins that help maintain the balance of proteins in the #cell, which is essential for the cell to stay alive. Chaperones are always present in the cell, but they can also be activated in response to #stress. They interact with proteins that are not folded correctly, preventing them from clumping together and helping them to fold correctly. Chaperones don't usually interact with proteins that are already folded correctly. They use #energy from #ATP binding and/or hydrolysis to help with #folding and unfolding proteins. Because chaperones are involved in keeping protein balance, they are linked to diseases caused by #protein misfolding, such as #neurodegeneration and #cancer. Therefore, understanding how chaperones work is important for understanding and treating these diseases.
The Hsp70 system is a group of proteins that are found in #bacteria, #eukaryotic cells, and some #archaea. They are responsible for binding to unfolded or partially unfolded proteins to prevent them from aggregating and to help them fold correctly. Hsp70 proteins are made up of two parts: a 44 kDa N-terminal ATPase domain and a 28 kDa substrate binding domain with a C-terminal lid subdomain. The #ATPase domain helps the protein bind and release substrates, while the substrate-binding domain binds to extended #polypeptide chains. Hsp40 proteins, which are also known as J-domain proteins, act as co-chaperones to Hsp70 and help recruit substrates and stimulate the ATPase activity of Hsp70. Hsp40s can also direct Hsp70 to specialized functions and sub-cellular regions.
Hsp90 is a type of molecular chaperone that helps proteins fold correctly. It is made up of three conserved domains: the ATP binding N-terminal domain, the middle domain, and the C-terminal dimerization domain. Hsp90 works by binding to proteins that need to be folded correctly and preventing them from aggregating in an ATP-dependent manner. It also interacts with other proteins, called co-chaperones, which help regulate its ATPase cycle and determine which proteins it binds to. Hsp90 can also act as a buffer for genetic variation by rescuing mutated proteins with altered properties.
The different functions of the Hsp100/Clp proteins.
These proteins contain one or two conserved ATPases Associated with various cellular Activities (AAA1) domains and can act as #unfoldases or #disaggregases. Unfoldases help to unfold proteins and deliver them to a ring #protease, while disaggregases have the unique ability to recover proteins from both amorphous and #amyloid aggregates. The main difference between the two is the presence of a coiled-coil insertion in the first AAA1 domain in the disaggregases. The Hsp100 proteins usually form hexamers which hydrolyze ATP in either a sequential/random or a concerted manner. #Crystal structures have been determined of monomeric forms of several Hsp100 proteins, and of the hexamer forms of HslU, ClpX, and ClpC unfoldases. Hexameric forms of various Hsp100’s have been observed at intermediate resolutions by cryo-EM. These structures suggest a typical AAA1 packing arrangement for the unfoldases and an expanded conformation for the Hsp104 disaggregase. The central channels of the Hsp100s are lined by tyrosine residues, located on mobile loops, which bind substrates non-specifically. It is thought that rotations of the AAA1 domains provide the force to unfold the bound substrate and pull it through the channel. Disaggregation and unfolding functions are coupled and regulated via an interaction between the Hsp70 nucleotide-binding domain and the coiled-coil insertion. Recent biochemical and structural data suggest that it is docked on the outside surface of the AAA1 ring. Hsp100/Clp proteins are proteins that have one or two conserved ATPases Associated with various cellular Activities (AAA1) domains. These proteins can act in two different ways: as unfoldases or disaggregases. Unfoldases help to unfold proteins and deliver them to a ring protease, while disaggregases have the ability to recover proteins from both amorphous and amyloid aggregates. The main difference between the two is the presence of a coiled-coil insertion in the first AAA1 domain in the disaggregases. The Hsp100 proteins usually form hexamers which hydrolyze ATP in either a sequential/random or a concerted manner. Structures of these proteins have been determined, which suggest a typical AAA1 packing arrangement for the unfoldases and an expanded conformation for the Hsp104 disaggregase. The central channels of the Hsp100s are lined by tyrosine residues, which bind substrates non-specifically. It is thought that rotations of the AAA1 domains provide the force to unfold the bound substrate and pull it through the channel. Disaggregation and unfolding functions are coupled and regulated via an interaction between the Hsp70 nucleotide-binding domain and the coiled-coil insertion, which is docked on the outside surface of the AAA1 ring.
GroEL is a molecular chaperone machine that binds to proteins to prevent them from aggregating. It is estimated that GroEL binds to around 10% of the proteins in E. coli. The binding site is hydrophobic in character and contains essential hydrophobic residues that line the cavity-facing surface of the apical domain. If one of these residues is changed from hydrophobic to hydrophilic, the binding is abolished. Studies have shown that multiple binding sites act together as a continuous hydrophobic binding surface. It has also been shown that proteins stably bound to #GroEL are unstructured and that binding of non-native proteins to GroEL can be associated with unfolding. X-ray crystallographic studies have revealed structures of extended or helical peptides bound in the groove formed by helices H and I via hydrophobic interactions. Cryo-EM has also been used to probe the structure of non-native proteins bound to GroEL, which showed that the substrates were bound to helices H and I, with substrate density protruding from the GroEL ring. There is an upper limit, around 60 kDa, to the size of substrate that can fit inside the folding chamber. In summary, GroEL is a molecular chaperone machine that binds to proteins to prevent them from aggregating. It has a hydrophobic binding site that contains essential hydrophobic residues. Studies have shown that multiple #binding sites act together as a continuous hydrophobic binding surface and that proteins stably bound to GroEL are unstructured. X-ray crystallographic and cryo-EM studies have revealed structures of extended or helical peptides bound in the groove formed by helices H and I via hydrophobic interactions. The upper limit to the size of substrate that can fit inside the folding chamber is around 60 kDa.
Structural, biochemical, and biophysical studies have shown how proteins interact with GroEL, a protein-folding machine, and how ATP (a molecule that provides energy for many processes in cells) induces changes in GroEL's shape that allow it to switch between binding to proteins and folding them. Mutational analysis and cryo-EM studies (a type of imaging technique) have revealed that proteins primarily bind to a specific part of GroEL, and that multiple parts of GroEL bind to the protein at the same time. This binding causes the parts of GroEL to extend and expand, which helps to unfold the protein. Additionally, the protein's binding to GroEL provides a mechanical load on GroEL, which helps to further unfold the protein. Finally, when ATP is added, the parts of GroEL rotate, which removes the binding sites from the inside of the chamber and traps the protein in the chamber, which is now capped by GroES (another protein-folding machine). Group 2 #chaperonins are similar to GroEL, but have a slightly different structure. They are found in both eukaryotes (organisms with a nucleus, like humans) and archaea (a type of single-celled organism). They form back-to-back rings and have a high degree of sequence identity/similarity to GroEL. The main difference is an extension in the part of GroEL that forms the lid of the folding chamber. This extension helps to further unfold the protein.
The structural similarities between the Group 2 chaperonins and GroEL, both essential for folding proteins. Group 2 chaperonins have 8- or 9-fold symmetry, meaning that they form back-to-back rings with the same domain structure and a high degree of sequence identity/similarity to GroEL. The main difference between the two is an extension in the helix H equivalent in the apical domain of the Group 2 chaperonin, which removes the need for a GroES co-chaperone. Structural studies of the Group 2 chaperonins in different nucleotide bound states have revealed open, substrate binding and closed, substrate folding conformations similar to GroEL. These conformations involve a large clockwise twist of the apical domains and an inward tilt of the whole subunit, which brings the catalytic Asp in the intermediate domain close to the ATP binding site and closes the folding chamber. The ring expansion/contraction of Group 2 chaperonins is facilitated by the 1:1 nature of their inter-ring interface, allowing the equatorial domains to move more freely than in GroEL.
ATP-driven chaperones are proteins that help other proteins maintain their structure and function. They do this by binding, unfolding, refolding, and disaggregating proteins that are not in their native state. The Hsp70 system uses ATP binding and hydrolysis to regulate the binding and release of substrates. It is also regulated by co-chaperones. Hsp90 uses its ATPase cycle to induce multiple conformations that bind and stabilize or help mature the substrate proteins. It is also regulated by co-chaperones. The Hsp100s use ATP to unfold, thread, and disaggregate substrate proteins. In ATP-dependent proteolysis, the unfoldase is connected to a protease which breaks down the unfolded substrate proteins. The disaggregases, in combination with the Hsp70 system, use ATP-induced conformational changes to disaggregate and unfold substrate proteins. GroEL-GroES uses ATP binding to induce conformational changes to convert from a substrate binding to a substrate folding complex. It may also use the ATP-induced conformational changes to force the substrate to unfold. GroES binding then ejects the substrate from the binding surface, giving it a chance to fold in isolation during the slow ATP hydrolysis step. The archaeal Group 2 chaperonins use ATP-induced domain rotations that are similar to GroEL, but the conformational changes are not in the same order. The eukaryotic cytosol Group 2 chaperonin is similar to the archaeal system, but its ATPase cycle and action appear to be more complex and specific to the substrate.
In conclusion, ATP-driven chaperones are proteins that help other proteins maintain their structure and function by binding, unfolding, refolding, and disaggregating proteins that are not in their native state. Structural studies of GroEL and Group 2 chaperonins have revealed ATP-induced conformational changes that bind, unfold, and refold proteins in the ATP-dependent folding process. GroEL uses ATP binding to induce a conformational change that switches between the substrate binding and substrate folding states. The archaeal Group 2 chaperonins have a similar mechanism, but with a different order of conformational changes. The eukaryotic cytosol Group 2 chaperonin is more complex, indicating different substrate-specific functions. In general, ATP-driven chaperones help to ensure the proper folding of proteins and support the lifecycle of proteins.
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#introduction
I'm an #earlycareer #sleep #neuroscientist aiming to understand why everything looks so much better in the morning.Currently a #postdoc with Matt Walker at #UC #berkeley working on the intersection of sleep with #aging & #mentalhealth.
Finished my #phd a year ago in #Faculty of #Medicine, #Tel-Aviv #university with Yuval Nir.
Worked on #sensory #perception during sleep, sleep & #memory and how it goes wrong in #Alzheimer.
#tau #amyloid #tvns #EEG, #psg #fMRI, #python #MNE -
CW: APOE in #Alzheimer's
This is what #EPAD and other studies are showing. #APOE4 is such a huge risk factor for #Alzheimer's (akin to a decade of ageing) that it's basically a different, #amyloid-heavy disease. There are other routes to #Tauopathy in those with e.g. E3/E3. Paper from the great and good here https://www.nature.com/articles/s41583-021-00533-w
But if Amyloid++ 4/4 genotypes predict best response AND worse SE to anti-Amyloid therapies, shouldn't we start to TEST for it and learn how best to communicate results?