Aβ₁–₄₂ (Amyloid-beta 1–42)

Name: Amyloid-beta (1–42) Abbreviation: Aβ₁–₄₂ Type: Peptide fragment Length: 42 amino acids Molecular weight: ~4.5 kDa Encoded by: APP (Amyloid precursor protein) gene

• Aβ₁–₄₂ is generated from the proteolytic cleavage of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase
• Exists in multiple conformations: monomers, oligomers, fibrils
• Aβ₁–₄₂ is more hydrophobic and prone to aggregation than Aβ₁–₄₀

• Major component of amyloid plaques found in Alzheimer’s disease (AD) brain tissue
• Neurotoxic, especially in its soluble oligomeric forms
• Impairs synaptic plasticity, induces oxidative stress, disrupts calcium homeostasis
• Oligomers may inhibit long-term potentiation (LTP) and memory formation

• Cerebrospinal fluid (CSF) Aβ₁–₄₂ levels are decreased in Alzheimer's disease due to plaque deposition
• Used in CSF biomarker panels:
  • ↓ Aβ₁–₄₂
  • ↑ Total tau (t-tau)
  • ↑ Phosphorylated tau (p-tau)
• Investigated in PET imaging (e.g., with radiotracers like Pittsburgh compound B)
• Animal models of AD often use intraventricular or hippocampal injection of synthetic Aβ₁–₄₂

• Target of anti-amyloid therapies, including:
  • Monoclonal antibodies (e.g., aducanumab, lecanemab)
  • Secretase inhibitors (limited success)
  • Aβ-clearance enhancers
• Immunotherapy against Aβ₁–₄₂ aims to prevent plaque formation and toxicity

• Aβ₁–₄₂/Aβ₁–₄₀ ratio is often more informative than absolute levels
• Accumulation precedes clinical symptoms by years or decades
• Ongoing debate: Amyloid hypothesis vs tau-first hypothesis in AD pathogenesis

• PubChem: Aβ₁–₄₂
• AlzForum: Aβ42 Biomarker
• NCBI: APP gene