TL;DR
Get health and wellness essentials delivered free with Prime
- Fast, free delivery on millions of items
- Prime Video, Amazon Music and more included
- Member-only deals all year
A commentary by UC Santa Cruz biochemist Jevgenij Raskatov highlights studies finding that P3, a peptide produced from the same precursor protein as amyloid beta, can form aggregates and may harm neurons. The findings challenge assumptions about P3, but do not establish that it causes or contributes to Alzheimer’s disease in patients.
A commentary published in ChemBioChem by University of California, Santa Cruz biochemist Jevgenij Raskatov argues that scientists should investigate P3, a peptide long regarded as harmless, after research found it can form aggregates and may damage neurons, adding to research into what may trigger Alzheimer’s disease. The findings raise a possible additional line of inquiry in Alzheimer’s research, but they do not show that P3 causes the disease in people.
P3 is produced when the amyloid precursor protein (APP) is cut by a different sequence of enzymes than the one that produces amyloid beta. In the P3 pathway, alpha-secretase acts before gamma-secretase. For years, researchers generally considered P3 unlikely to accumulate because it was thought to remain soluble and not form amyloid-like deposits.
Raskatov’s laboratory has published three studies over the past five years reporting that P3 can form microscopic clumps and threadlike fibrils. In the team’s experiments, P3 formed aggregates more rapidly than amyloid beta. The researchers also reported evidence that P3 may be toxic to neurons, although its apparent toxicity was lower than amyloid beta’s.
The commentary says an independent research group in the United Kingdom has confirmed and extended aspects of the findings. Researchers are also beginning to examine whether P3 interacts with amyloid beta and whether that interaction affects how either peptide accumulates or harms cells. Those questions remain under investigation; the laboratory results alone do not establish P3’s role in Alzheimer’s disease in patients, or explain how Alzheimer’s spreads through the brain.
A Wider Search for Alzheimer’s Mechanisms
The work matters because amyloid beta has dominated Alzheimer’s drug research for decades, yet treatments aimed at it have delivered limited benefits so far. According to the source report, more than 400 clinical trials have examined potential Alzheimer’s drugs, most focused on amyloid beta. Some drugs have failed, while others have shown modest benefit; certain treatments have also been associated with serious complications, including brain hemorrhages and strokes.
If P3 is shown to affect disease processes in people, researchers may need to account for it when studying the biology of amyloid buildup or designing future therapies. That is a research possibility, not a clinical conclusion. No evidence in the cited work establishes that targeting P3 would prevent, treat, or slow Alzheimer’s, and the commentary does not change current treatment guidance.
Alzheimer's research peptide aggregates
As an affiliate, we earn on qualifying purchases.
As an affiliate, we earn on qualifying purchases.
How P3 Differs From Amyloid Beta
Both peptides come from APP, a protein embedded in cell membranes, but they are generated through different processing routes. Beta-secretase followed by gamma-secretase produces amyloid beta peptides, including Aβ40 and Aβ42. Aβ42 has received particular attention because it readily clumps together. Alpha-secretase followed by gamma-secretase produces P3, which was long treated as a soluble byproduct rather than a potentially aggregating peptide.
Alzheimer’s research has also produced treatments that address symptoms without stopping disease progression. More recently approved antibody treatments, including lecanemab and donanemab, are designed to remove amyloid beta from the brain. Raskatov says their benefits remain limited and argues for examining additional biological processes. His commentary proposes the name “Amyloid alpha,” or Aα, for P3 to distinguish it from amyloid beta and reflect its reported capacity to aggregate.
“The P3 peptide is, most likely, not the innocent bystander it was commonly thought to be.”
— Jevgenij Raskatov, UC Santa Cruz professor
P3’s Role in Patients Is Unknown
The reported experiments show that P3 can aggregate under laboratory conditions and may harm neurons, but they do not establish whether P3 accumulates in the brains of people with Alzheimer’s or contributes to the disease’s onset or progression. The extent and conditions of any interaction with amyloid beta also remain unsettled.
Further independent work is needed to test the findings, clarify how the peptides behave in biological settings, and determine whether any observed effects are relevant to patients. The source report does not describe clinical evidence linking P3 levels to disease outcomes, nor does it report a P3-targeting treatment.
Research Must Test the Peptide
The next step is further laboratory and independent research into P3 aggregation, neuronal effects, and interactions with amyloid beta. Studies will need to establish whether these processes occur in relevant biological settings and whether they are associated with Alzheimer’s in people. Until that evidence is available, P3 remains a potential research lead rather than a confirmed disease driver or treatment target.
Key Questions
What is P3?
P3 is a peptide made from amyloid precursor protein when the protein is processed through an alpha-secretase and then gamma-secretase pathway. That differs from the pathway that produces amyloid beta.
What did the research report find?
Raskatov’s team reported that P3 can form aggregates and may be toxic to neurons. Its apparent toxicity was lower than amyloid beta’s in the experiments described. These findings do not establish an effect in patients.
Does P3 cause Alzheimer’s disease?
That has not been established. The commentary raises the possibility that P3 could contribute, but further research is needed to determine whether it plays a role in people with Alzheimer’s.
Could P3 lead to a new Alzheimer’s treatment?
It is too early to know. Researchers first need to establish whether P3 is relevant to the disease in patients. No P3-targeting treatment is reported in the source material.
Source: rss
Fall Picks
fall essentials
As an affiliate, we earn on qualifying purchases.
