Q60 — Alzheimer's Disease — APP Processing by α-, β- and γ-Secretases

Theoretical 2 Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license

Alzheimer’s disease is related to the aggregation of amyloid peptides, followed by the degeneration of neurons and disruption of cholinergic transmission. Among patients suffering from Alzheimer’s disease, the β-amyloid peptides (Aβ) are formed from the cleavage of the protein APP. The normal protein (APP) is composed of many α-helices, making it highly soluble. The β-amyloid, in contrast, has a secondary structure rich in β-sheets, which aggregate easily and create insoluble fibers. APP is a multi-domain transmembrane protein. There are three proteases, which take part in the proteolytic processing of APP: α-, β-, and γ-secretases.

Figure 1. APP multi-domain protein modification — β-cleavage followed by γ-cleavage releases the amyloidogenic Aβ peptide (red); α-cleavage (which cuts within the Aβ sequence) followed by γ-cleavage instead releases non-amyloidogenic fragments (teal), precluding Aβ formation. Figure 1. APP multi-domain protein modification by α-, β- and γ-secretases.

Determine whether the following statements are true or false:

A. α-secretase cleaves the mature APP in a certain location and, thus, prevents the formation of β-amyloid.

B. β- and γ-secretases take part in the formation of the β-amyloid peptide.

C. Two transmembrane protein fragments are formed due to α-secretase activity: the N-terminal fragment and the C-terminal fragment.

D. In the C-terminal transmembrane fragment, formed due to α-secretase activity, the α-helical structure dominates.

← Previous: Q59 Next: Q61 →

Question reproduced from IBO 2022, Theoretical Paper 2, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)