====== 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  

===== 🧬 Origin and Structure =====
  * 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  

===== 🧠 Biological and Clinical Significance =====
  * 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

===== 🧪 Diagnostic and Research Use =====
  * **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

===== 💊 Therapeutic Implications =====
  * 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  

===== ⚠️ Pathophysiological Notes =====
  * **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  

===== 📚 References =====
  * [[https://pubchem.ncbi.nlm.nih.gov/compound/133304|PubChem: Aβ₁–₄₂]]  
  * [[https://www.alzforum.org/alzbiomarker/amyloid-beta-42|AlzForum: Aβ42 Biomarker]]  
  * [[https://www.ncbi.nlm.nih.gov/gene/351|NCBI: APP gene]]