Oil Palm Phenolics Inhibit the Aggregation of -Amyloid Peptide into Oligomeric Complexes.

Alzheimer’s disease is a severe neurodegenerative disease characterized by the aggregation of amyloid- peptide (A) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of A42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that A42 aggregation is inhibited by oil palm phenolics (OPP), an aqueous extract from the oil palm tree . The data shows that OPP inhibits stacking of -pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of A42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of A into oligomers; (2) stacking of -pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer’s disease.