UC Santa Barbara

Alzheimer’s disease (AD) affects over 40 million people worldwide: a number that is expected to grow to over 100 million by 2050.1 Despite this, there is a shortage of AD drugs on the market, with only five having been FDA approved, and no new ones since 2003.2 A major problem is that these drugs are merely symptomatic treatments. No drugs exist that stop or prevent AD. One of the hallmarks of AD are intracellular deposits of insoluble neurofibrillary tangles (NFTs) in neurons of the brain.3 NFTs are composed of aggregates of the microtubule-associated protein, tau. This study focuses on discovering novel treatments that prevent the aggregation of tau.

Peanut skins contain large amounts of procyanidins4: molecules proposed to have various health benefits.5 Peanut skin extract was run through high performance liquid chromatography (HPLC) to separate the many compounds present, in order to isolate procyanidin molecules. One particular procyanidin was separated and used for inhibition assays with tau and appeared to inhibit its aggregation into NFTs. It was then identified using electrospray ionization mass spectrometry (ESI-MS) and proton nuclear magnetic resonance (1H-NMR) to be the A1 procyanidin dimer isomer.

While running HPLC to isolate more procyanidin A1 for further experimentation, it became apparent that one of the pumps had a leak. This caused a lower percentage of that pump’s solvent to go through the column than what it was set to. This resulted in the presumably pure procyanidin A1 eluting later than usual, and separating from another, currently unidentified, molecule. Further experimentation led to the conclusion that the A1 procyanidin has no effect on the aggregation of tau, which was backed up by tests that were then done with a commercially available procyanidin A1 that was purchased. It is assumed that an unidentified contaminant is responsible for the inhibitory activity. Further studies are required to find which compound is responsible for the inhibition seen on tau aggregation.