Paper Title
Clinical Treatment of Alzheimer’s Disease: Gaps and Alternative Multidimensional Approach of Biophenols

Alzheimer's disease (AD) is one of the most common neurodegenerative disease, clinically characterized by severe deficit in memory, cognitive impairment, and personality disorders in the aged population. The pathophysiological changes accompanied by protein aggregates including amyloid beta, phosphorylated tau, and rise in oxidative stress and depletion in acetylcholine levels in the brain. Since, three decades, clinical sciences are unable to reach cure for Alzheimer's disease, however, mainly four FDA-approved drugs available three from cholinesterase inhibitors to boost acetylcholineand one from glutamate inhibitor through activating NMDA receptor-memantine. Unfortunately, these drugs are not for curative and are unable to stop the disease progression from worsening over time.Accumulated evidences of dietary intervention in animal and clinical studies reported the inverse correlation between plant biophenols consumption and the incidence of AD. Several phenolic compounds (biophenols) including epigallocatechin gallate, curcumin, resveratrol, oleuropein, quercetin, hydroxytryrosol, rutin, and verbascoside have been extensively investigated either alone or in the form of extracts and showed significant anti-amyloid, anti-tau, antioxidant, cholinesterase and β-secretase inhibitory activitiesin the range of IC50 0.01-100 μM. Furthermore, the beneficial mechanisms of biophenols against age-related cognitive decline and ADare precisely not known, while suggested through modulating signalling pathways, reducing neuroinflammation, promoting vascular effects that can stimulate new nerve cell growth in the hippocampus, altering amyloid oligomer formation via changing oligomer size distribution and/or modulating oligomer conformation. Increasing consensus that multiple mechanisms are involved during aging may synergistically contribute to AD pathogenesis and cognitive decline, therefore it is important to continue investigating the role of combination therapies including the efficacy and bioavailability in brain. Keywords - Alzheimer’s Disease, Amyloid Beta, Phosphorylated Tau, Biophenols, Antioxidants.