![\"Headshot](\"https:\/\/www.newsbeep.com\/il\/wp-content\/uploads\/2026\/02\/jevgenij-raskatov-headshot-1024x1024.jpg\")
Jevgenij Raskatov<\/p>\n
\u201cThe P3 peptide is, most likely, not the innocent bystander it was commonly thought to be. There\u2019s still more research to be done. But this could turn Alzheimer\u2019s research on its head,\u201d said Raskatov, whose lab researches amyloid peptides to discover new ways to block toxicity and inform better therapeutics for Alzheimer\u2019s patients. \u201cP3 is a distinct aggregating peptide that is itself potentially neurotoxic and may be contributing to Alzheimer\u2019s disease.\u201d<\/p>\n
Limitations of targeting Amyloid beta<\/p>\n
The disease is the world\u2019s most common neurodegenerative disorder, afflicting about 35 million people globally and costing in excess of $800 billion annually. The patient estimate is projected to double by 2050. Meanwhile, the majority of the more than 400 clinical trials for Alzheimer\u2019s drugs targeted A\u03b2 and mostly failed\u2014or showed only modest results while triggering serious side effects such as hemorrhages and strokes.<\/p>\n
The A\u03b2 peptide is produced when a much larger precursor transmembrane protein in the brain, called the Amyloid Precursor Protein (APP), is sequentially cleaved by the enzymes \u03b2-secretase and then \u03b3-secretase. This produces peptides of varied length, with the ones containing 40 and 42 amino acids receiving the most attention. They are commonly referred to as A\u03b240 and A\u03b242\u2014the latter peptide being substantially more aggregation-prone and toxic, and hence, the principal therapeutic target for Alzheimer\u2019s drugs for decades.<\/p>\n
Current treatments include cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, which offer temporary relief of symptoms but do not slow the disease\u2019s progression. Recently approved antibody therapies targeting A\u03b2, including Lecanemab and Donanemab, were designed to clear the beta peptide from the brain.<\/p>\n
But Raskatov said they\u2019ve shown limited success to date. \u201cProgress has been extremely slow, and the current state of the art in Alzheimer\u2019s therapy leaves much to be desired,\u201d he said. \u201cWe need fundamentally new approaches to the problem.\u201d<\/p>\n
P3 a.k.a. \u2018Amyloid alpha\u2019<\/p>\n
The P3 peptide is the alternative major processing product of the same Amyloid Precursor Protein being cleaved, but instead by the enzymes \u03b1- and then \u03b3-secretase. Raskatov has dubbed this isoform \u201cAmyloid \u03b1,\u201d or A\u03b1, to help avoid confusion with regard to its properties. Previous studies erroneously assumed, without verification, that this peptide was non-amyloidogenic, non-toxic, and water soluble, and so would eventually dissolve in the brain.<\/p>\n
As a result, P3 went understudied and was subsequently dismissed as irrelevant to Alzheimer\u2019s disease. But as a peptide chemist, Raskatov and members of his lab decided to interrogate convention. They published three major manuscripts over the past five years demonstrating unambiguously that P3 is at least as capable as A\u03b2 of forming amyloid deposits\u2014and producing them more rapidly.<\/p>\n
Finally, they found that P3 is itself potentially toxic to neurons, albeit less so than A\u03b2. Raskatov said their results were validated and extended by an independent laboratory in the UK, adding that studies from other labs aimed to better understand the interactions between A\u03b2 and A\u03b1 are beginning to emerge.<\/p>\n
Overcoming scientific dogma<\/p>\n
David Teplow, an emeritus professor of neurology at UCLA and a leading Alzheimer\u2019s researcher, said A\u03b2 has been believed to be the culprit of the disease for decades. In an independent assessment of Raskatov\u2019s work, Teplow said this is now changing.<\/p>\n
\u201cThis reevaluation has far-reaching consequences for both basic science and clinical research into the causes and treatment of Alzheimer\u2019s disease,\u201d said Teplow, a founding editorial board member of the Journal of Molecular Neuroscience, the American Journal of Neurodegenerative Disease, and editor-in-chief of Progress in Molecular Biology and Translational Science.<\/p>\n
When reviewing recent research by others, Raskatov said he has at times been quite shocked. He has found at least four scientific articles published in respectable peer-reviewed journals, citing his lab\u2019s work as evidence that P3 is innocuous and does not form amyloid.<\/p>\n
\u201cThis is exactly the opposite of what we have actually shown,\u201d Raskatov said. \u201cWe remain in the dark on how this sort of grand confusion may have come about. Clearly, there is more work ahead of us.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Key takeaways A new culprit: While billions of dollars have been spent targeting Amyloid beta (A\u03b2) in Alzheimer\u2019s…\n","protected":false},"author":2,"featured_media":313878,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46,1360],"class_list":["post-313877","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel","tag-research"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/313877","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=313877"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/313877\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/313878"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=313877"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=313877"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=313877"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}