Table 1.

Schematic representation of APP structure and function.

APP structural regions	Location	Function	Primary papers
E1	exons 1-5: amino acid residues 18-189 (GFLD; CuBD)	hydroxyl radical production, APP dimerization and synaptic adhesion	[24-26]
AcD	exons 6: amino acid residues 191-291	unfolded and highly flexible, and directly links E1 to E2	[26]
KPI	exons 7: amino acid residues 292-341	be relevant to metabolic enzymes, mitochondrial function and cell growth	[20-23]
OX-2	exons 7-8: amino acid residues 344-365	cell-surface binding and recognition	[20]
E2	exons 9-14: amino acid residues 374-565 (HBD; RERMS; )	trophic functions	[31-35]
JMD	exons 14-17: amino acid residues 366-700	Contains the cleavage sites for α-secretase and β-secretase	[36]
Aβ	exons 16-17: amino acid residues 671-712	Regulates neuronal homeostasis; abnormally aggregated forms of Aβ oligomers and plaques;	[41-43]
TMD	exons 17: amino acid residues 701-723	γ-secretase cuts; Directly interacts with cholesterol; modulates APP processing;	[39,40]
AICD	exons 17-18: amino acid residues 724-770	transcriptional regulator;leads to hippocampal degeneration, tau phosphorylation and deficits in working memory	[44-51]

AcD: acidic domain; KPI: Kunitz protease inhibitor; OX-2: Ox-2 antigen domain; JMD: juxtamembrane domain; TMD: transmembrane domain; AICD: APP intracellular domain; GFLD: growth factor-like domain; CuBD: copper-/metal-binding domain; HBD: heparin-binding domain; RERMS (amino acids 328-332) was uniquely required for the growth-promoting activity of sAPP-695.