Beta-Amyloid (4-42)

Product Name: Beta-Amyloid (4-42)

Sequence One Letter Code: FRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA

Sequence Three Letter Code: H-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala-OH

Chemical Formula:C191H294N52O53S

Molecular Weight: 4198.8

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: Beta-Amyloid (4–42) is an N-terminally truncated amyloid-β peptide identified as a major component of Alzheimer’s disease plaques. This variant is highly abundant in the AD brain and exhibits pronounced aggregation behavior compared with several full-length Aβ species. Aβ4–42 rapidly self-associates, demonstrating efficient monomer consumption and formation of soluble oligomers and higher-order assemblies. These oligomeric intermediates are strongly implicated in synaptic dysfunction and neurotoxicity. The peptide’s structural properties make it a valuable model for studying the impact of N-terminal truncation on aggregation kinetics, conformational stability, and pathogenic potential. Beta-Amyloid (4–42) is widely applied in biochemical, biophysical, and cellular assays to investigate structure–toxicity relationships and plaque development mechanisms. It supports mechanistic studies exploring amyloid heterogeneity, neuronal vulnerability, and therapeutic interventions targeting early aggregation events in Alzheimer’s disease progression.

Current Research: Beta-Amyloid (4–42) is an N-terminally truncated amyloid-β (Aβ) peptide recognized as a prominent and highly pathogenic species in Alzheimer’s disease (AD). Unlike the canonical Aβ1–40 and Aβ1–42 isoforms generated through sequential cleavage of amyloid precursor protein, Aβ4–42 lacks the first three N-terminal residues. This truncation significantly alters its biochemical behavior and has been consistently identified as a major component of amyloid plaques in the AD brain. Current research increasingly highlights Aβ4–42 as one of the most aggregation-prone Aβ variants. The absence of the initial N-terminal residues modifies charge distribution and structural flexibility, promoting rapid self-association. In vitro studies demonstrate efficient monomer consumption and accelerated formation of soluble oligomers, protofibrils, and mature fibrillar assemblies. Compared with several full-length Aβ species, Aβ4–42 often exhibits enhanced aggregation kinetics and increased conformational stability of its β-sheet–rich structures. Of particular interest is the formation of soluble oligomeric intermediates. These species are widely regarded as primary mediators of synaptic dysfunction and neuronal toxicity in AD. Aβ4–42 readily forms low-n oligomers that disrupt synaptic signaling, impair long-term potentiation, and induce cellular stress responses. Experimental models suggest that even before extensive plaque deposition occurs, truncated peptides such as Aβ4–42 may contribute to early cognitive decline by interfering with neuronal communication. Biophysical characterization of Aβ4–42 commonly involves circular dichroism spectroscopy, thioflavin-based fluorescence aggregation assays, dynamic light scattering, and electron microscopy. These techniques reveal rapid secondary structure transitions toward β-sheet–dominated conformations and the formation of structurally stable aggregates. The peptide’s reproducible aggregation profile makes it a robust model for investigating how N-terminal truncation influences nucleation, elongation, and fibril architecture. Importantly, Aβ4–42 provides a comparative framework for analyzing amyloid heterogeneity. Alzheimer’s disease plaques are composed of a mixture of full-length and truncated Aβ species, and their interactions may influence overall aggregation dynamics and toxicity. Studies indicate that truncated peptides can act as seeds, accelerating aggregation of other Aβ isoforms. Understanding these cross-seeding mechanisms is essential for clarifying how diverse amyloid populations contribute to plaque maturation and disease progression. In cellular systems, exposure to Aβ4–42 induces oxidative stress, mitochondrial dysfunction, and activation of pro-inflammatory signaling pathways. Neuronal cultures treated with this peptide exhibit reduced viability and altered synaptic protein expression. Such findings support the hypothesis that truncated Aβ variants play a direct role in neurodegenerative processes rather than representing passive byproducts of amyloid processing. The peptide is also widely used in therapeutic research aimed at targeting early aggregation events. Because Aβ4–42 aggregates rapidly and forms stable oligomers, it serves as a stringent model for evaluating small molecules, antibodies, or peptide-based inhibitors designed to block nucleation or disrupt oligomer formation. Screening strategies often rely on kinetic aggregation assays to quantify inhibitor efficacy and characterize mechanism of action. Beyond aggregation studies, Aβ4–42 supports mechanistic investigations into proteolytic processing pathways that generate truncated Aβ species. Elucidating how these variants arise in vivo may reveal upstream enzymatic targets for intervention. By modeling both structural and functional consequences of truncation, researchers gain deeper insight into how specific Aβ forms influence neuronal vulnerability. Overall, Beta-Amyloid (4–42) is a highly relevant experimental tool for Alzheimer’s disease research. Its pronounced aggregation behavior, oligomer stability, and neurotoxic potential make it indispensable for studying structure–toxicity relationships and plaque development mechanisms. Through detailed biochemical, biophysical, and cellular analyses, Aβ4–42 continues to advance understanding of amyloid diversity and its role in neurodegeneration.