Therapeutic Potential of Polyphenols in Alzheimer’s Therapy: Broad-Spectrum and Minimal Side Effects as Key Aspects

Alzheimer’s disease (AD) is a degenerative brain disease that is the leading cause of dementia among the human population. AD is characterized by accumulating amyloid plaques which are insoluble deposits of a 4 kDa peptide of ~40–42 amino acids in length, known as amyloid-β (Aβ). The imbalance between Aβ generation and clearance in the brain leads to the progression of AD. AD pathology is characterized by the deposition of oligomeric and fibrillar forms of amyloid-β (Aβ) in the neuropil and cerebral vessel walls. Neurofibrillary tangles are composed mainly of hyperphosphorylated tau and neurodegeneration. Polyphenols are the most abundant antioxidants in the diet. More than 8000 naturally occurring polyphenols exist. Numerous studies have indicated that high consumption of fruits and vegetables rich in flavonoids and other polyphenols reduces the risk/incidence of age-related neurodegenerative disorders, highlighting the importance of these polyphenols as neuroprotective agents. Due to polyphenols’ ability to influence and modulate multiple targets in the cascade of the pathogenesis of neurodegenerative diseases, they are considered a candidate with a promising result against neurodegeneration, halting the progression of the disease. There is now substantial evidence indicating that oxidative damage to the brain is an early AD pathogenesis event. Oxidative stress and damage to brain macromolecules are vital processes in neurodegenerative diseases. The antioxidant properties of many polyphenols are purported to provide neuroprotection. There are pieces of evidence that some of the polyphenols can easily cross the blood-brain barrier (BBB). This chapter will provide deeper insights into various polyphenols that play a pivotal role in AD and shed light on the roles of these in the context of AD therapeutics.