[Gly21]-beta-Amyloid (1-40), A21G, Flemish Mutation

Product Name: [Gly21]-beta-Amyloid (1-40), A21G, Flemish Mutation

Sequence One Letter Code: DAEFRHDSGYEVHHQKLVFFGEDVGSNKGAIIGLMVGGVV

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

Cas No: 154362-03-5

Chemical Formula:C193H293N53O58S

Molecular Weight: 4316.1

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

SMILES: COC1=C(C=CC(=C1)C#N)C2=NC=C(C3=C2C=CC(=C3)S(=O)(=O)NC4=NC=NS4)F

IUPAC: 1-(4-cyano-2-methoxyphenyl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

INCHIKEY: DWAXYXVPNJLGHQ-UHFFFAOYSA-N

INCHI:

InChI=1S/C19H12FN5O3S2/c1-28-17-6-11(8-21)2-4-14(17)18-13-5-3-12(7-15(13)16(20)9-22-18)30(26,27)25-19-23-10-24-29-19/h2-7,9-10H,1H3,(H,23,24,25)

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: [Gly21]-β-Amyloid (1–40), also known as the A21G or Flemish mutation, is a disease-associated variant of the amyloid-β peptide linked to autosomal dominant Alzheimer’s disease. Unlike many familial mutations that strongly accelerate aggregation, the Flemish variant displays relatively low intrinsic aggregation propensity while still promoting progressive amyloid deposition in cerebral vessel walls. Pathology associated with this mutation is characterized by the predominance of Aβ1–40 in vascular deposits rather than the Aβ1–42 species typically observed in Alzheimer’s plaques. Because of these unique features, the peptide provides an important model for studying mutation-specific amyloid behavior and cerebral amyloid angiopathy. It supports research into vascular contributions to Alzheimer’s disease and mechanisms of amyloid deposition in the brain.

Current Research: Amyloid-β (Aβ) peptides play a central role in the pathology of Alzheimer’s disease (AD) and related neurodegenerative disorders. These peptides are generated through proteolytic cleavage of the amyloid precursor protein (APP) and can aggregate to form amyloid deposits in the brain. While most Alzheimer’s cases are sporadic, certain familial mutations in the Aβ sequence are associated with inherited forms of the disease. One such variant is [Gly21]-β-Amyloid (1–40), also known as the A21G or Flemish mutation, which is linked to autosomal dominant Alzheimer’s disease and is strongly associated with cerebral amyloid angiopathy (CAA). Unlike many other familial Aβ mutations that dramatically accelerate peptide aggregation, the Flemish variant displays distinct aggregation behavior and produces a unique pathological pattern in the brain. As a result, this peptide has become an important research model for understanding mutation-specific amyloid biology and vascular contributions to neurodegeneration. Amyloid-β Peptides in Alzheimer’s Disease Amyloid-β peptides are produced through sequential cleavage of the amyloid precursor protein by β-secretase and γ-secretase enzymes. The two most common forms generated are Aβ1–40 and Aβ1–42, which differ by two amino acids at the C-terminus. These peptides can misfold and aggregate into oligomers, protofibrils, and fibrillar amyloid deposits. Accumulation of these aggregates in brain tissue is a hallmark of Alzheimer’s disease pathology. While Aβ1–42 is often associated with the formation of senile plaques within brain parenchyma, Aβ1–40 is more commonly linked to amyloid deposition in cerebral blood vessels. Genetic mutations within the Aβ sequence can influence how these peptides fold, aggregate, and interact with surrounding tissues, leading to different disease phenotypes. The Flemish Mutation: A21G Substitution The Flemish mutation involves a substitution of glycine for alanine at position 21 of the Aβ sequence. This single amino acid change alters the structural and aggregation properties of the peptide. Compared with many other familial Alzheimer’s mutations, the A21G variant exhibits relatively low intrinsic aggregation propensity. In vitro studies often show slower formation of amyloid fibrils compared with wild-type peptides or other aggressive variants. Despite this reduced aggregation tendency, individuals carrying the mutation still develop progressive amyloid accumulation in cerebral vasculature. This paradox highlights the complex relationship between peptide aggregation kinetics and disease pathology. Association with Cerebral Amyloid Angiopathy One of the defining characteristics of the Flemish mutation is the predominance of amyloid deposition within cerebral blood vessel walls, a condition known as cerebral amyloid angiopathy (CAA). In these cases, vascular amyloid deposits consist mainly of Aβ1–40, rather than the Aβ1–42 species typically found in parenchymal plaques. CAA contributes to vascular dysfunction and increases the risk of intracerebral hemorrhage and cognitive decline. Because the Flemish mutation produces pronounced vascular amyloid accumulation, it provides a valuable model for investigating how amyloid deposition affects cerebrovascular integrity. Research using this peptide helps clarify how amyloid interacts with vascular cells, extracellular matrix components, and blood–brain barrier structures. Studying Mutation-Specific Amyloid Behavior The unique characteristics of [Gly21]-β-Amyloid (1–40) make it useful for studying how subtle sequence variations influence amyloid structure and disease progression. Researchers often compare this peptide with other Aβ variants to understand how mutations affect: Peptide aggregation kinetics Formation of oligomers and fibrils Interaction with vascular and neuronal cells Patterns of amyloid deposition in brain tissue These comparisons help reveal how structural changes in Aβ peptides contribute to different clinical and pathological outcomes. Applications in Alzheimer’s and Neurovascular Research The Flemish Aβ variant is widely used in experimental studies focused on the vascular aspects of neurodegeneration. Common research applications include: Investigating mechanisms of cerebral amyloid angiopathy Studying mutation-dependent amyloid aggregation behavior Examining interactions between amyloid peptides and vascular endothelial cells Exploring the role of vascular amyloid in neuroinflammation and neurodegeneration These studies contribute to a broader understanding of how vascular pathology intersects with classical Alzheimer’s disease mechanisms. Insights into Vascular Contributions to Alzheimer’s Disease Growing evidence suggests that vascular dysfunction plays a significant role in Alzheimer’s disease progression. Amyloid deposition within blood vessel walls can impair cerebral blood flow, disrupt the blood–brain barrier, and trigger inflammatory responses that exacerbate neuronal damage. Because the Flemish mutation produces pronounced vascular amyloid accumulation, it offers a valuable model for examining the relationship between amyloid pathology and cerebrovascular health. Understanding these interactions may help identify new therapeutic strategies aimed at targeting vascular amyloid deposition or improving cerebral vascular resilience. Supporting Research on Amyloid Pathology The [Gly21]-β-Amyloid (1–40) peptide provides researchers with a well-defined mutation associated with inherited Alzheimer’s disease and cerebral amyloid angiopathy. Its distinctive aggregation profile and vascular deposition pattern make it particularly useful for investigating mutation-specific mechanisms of amyloid pathology. By enabling controlled studies of amyloid behavior and vascular amyloid accumulation, this peptide continues to support advances in research exploring Alzheimer’s disease, cerebral amyloid angiopathy, and the vascular factors contributing to neurodegenerative disorders.