Proteins implicated in Alzheimer’s disease Which protein (historically termed A4) is directly associated with amyloid plaque formation in Alzheimer’s disease?
-
AA4 (amyloid precursor protein–derived peptide, amyloid-β)
-
BAmylin (islet amyloid polypeptide)
-
CFibrin
-
D“Alzhemin” (nonexistent term)
-
EAlpha-synuclein
Answer
Correct Answer: A4 (amyloid precursor protein–derived peptide, amyloid-β)
Explanation
Introduction / Context:Alzheimer’s disease features extracellular amyloid plaques and intracellular neurofibrillary tangles. The plaque core contains amyloid-β (Aβ) peptides derived from the amyloid precursor protein historically called the A4 precursor.
Given Data / Assumptions:
- Aβ peptides (≈40–42 aa) derive from APP via beta- and gamma-secretase cleavage.
- Terminology “A4” reflects older literature naming APP as A4 precursor protein.
Concept / Approach:Link historical term “A4” to the modern understanding of Aβ/APP. Differentiate from proteins associated with other disorders.
Step-by-Step Solution:
Identify that A4 refers to APP/Aβ context.Select the option indicating amyloid-β derived from APP.Exclude proteins linked to other diseases.Verification / Alternative check:Neuropathology consistently identifies Aβ as the major plaque component, confirming the association.
Why Other Options Are Wrong:
- Amylin: aggregates in type 2 diabetes islet amyloid, not Alzheimer’s plaques.
- Fibrin: coagulation protein; not the etiologic plaque protein.
- “Alzhemin”: not a recognized protein.
- Alpha-synuclein: implicated in Parkinson’s/Lewy body disease.
Common Pitfalls:Confusing various amyloid-forming proteins across diseases; the context and tissue specificity are key.
Final Answer:A4 (amyloid precursor protein–derived peptide, amyloid-β)