**Question:** In Alzheimer's disease, the plaque is made up of: (E. REPEAT 2010)

**Core Concept:** Alzheimer's disease is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. The plaques found in Alzheimer's are extracellular aggregates of amyloid-beta (Aβ) peptides, which are derived from the amyloid precursor protein (APP) through a series of proteolytic cleavages by β-secretase (BACE1) and γ-secretase enzymes.

**Why the Correct Answer is Right:** Alzheimer's disease is primarily caused by the accumulation of amyloid-beta peptides in extracellular plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein. The correct answer (D) refers to the amyloid-beta peptides, which are formed through the cleavage of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase enzymes.

**Why Each Wrong Option is Incorrect:**

A. This option refers to tau protein, which is involved in forming neurofibrillary tangles in Alzheimer's disease. However, it does not address the primary component of Alzheimer's plaques.

B. This option mentions the amyloid precursor protein (APP), which is the source of amyloid-beta peptides in Alzheimer's disease. However, it does not explain the actual component of the plaque (amyloid-beta peptides).

C. This option discusses the γ-secretase enzyme, which is involved in APP cleavage but does not specifically address the amyloid-beta peptides as the primary component of Alzheimer's plaques.

**Clinical Pearl:** Understanding the molecular pathophysiology of Alzheimer's disease is crucial for the proper diagnosis and management of patients with cognitive decline, as well as for drug development targeting amyloid-beta peptides and tau protein.

**Correct Answer:** Alzheimer's disease is primarily caused by the extracellular accumulation of amyloid-beta peptides in extracellular plaques, which are formed through the cleavage of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase enzymes.