Platelets and Alzheimer’s disease: Potential of APP as a biomarker

Figure 1 Schematic diagram of the amyloid precursor protein. The diagram represents the structural domain arrangement of the amyloid precursor protein (APP) gene products. All domains are expressed in the APP₇₇₀ isoform. The OX-2 domain is missing in APP₇₅₁, whereas both the Kunitz protease inhibitor domain (KPI) and the OX-2 domain are missing in APP₆₉₅. SP: Signal peptide; E1: Ectodomain 1; E2: Ectodomain 2; TMD: Transmembrane domain; CD: Cytosolic domain; OX-2: Domain with homology to OX-2 leukocyte antigen; Ex 15: Exon 15 product; HB: Heparin-binding domain; MB: Metal ion-binding domain.

Figure 2 Proteolytic processing of amyloid precursor protein by the secretases. In a non-amyloidogenic pathway, α-secretase cleaves amyloid precursor protein (APP) within the Aβ domain to release the α-cleaved soluble N-terminal fragment, sAPPα. β-Amyloid precursor cleaving enzyme (BACE) cleaves APP at the N-terminus of Aβ to release the β-cleaved soluble N-terminal fragment sAPPβ, and thereby initiates the amyloidogenic pathway. The remaining 99 amino acid-long C-terminal fragment (C99) is further processed at multiple sites by γ-secretase to release the APP intracellular domain (AICD) in the cytosol and Aβ peptides in the extracellular space.