Which peptide fragment is derived from the amyloid precursor protein and accumulates extracellularly in Alzheimer's disease?

• A. Tau protein
• B. Prion protein
• C. Beta-amyloid (Aβ) peptide
• D. Alpha-synuclein

Answer: (C)

Beta-amyloid peptide is the fragment produced from the amyloid precursor protein and is the one that accumulates outside neurons in Alzheimer's disease. APP is a transmembrane protein; when it’s cleaved by beta-secretase followed by gamma-secretase, it releases Aβ fragments, especially Aβ42, which tend to aggregate and form extracellular amyloid plaques. These plaques disrupt neuronal signaling and provoke inflammation, contributing to neurodegeneration. Other proteins listed are involved in different disease processes: tau accumulates intracellularly as neurofibrillary tangles, prion protein misfolding drives prion diseases, and alpha-synuclein forms Lewy bodies in Parkinson disease. Thus, the extracellular accumulation of beta-amyloid derived from APP is characteristic of Alzheimer's pathology.