Amyloid Beta and Tau: from Physiology to Pathology in Alzheimer's Disease

Alzheimer’s disease (AD), as the most common age-related neurodegenerative disease, affects 2% of general elderly populations. Amyloid plaques and neurofibrillary tangles are two main hallmarks of AD that are usually associated with cerebral amyloid angiopathy. Imbalance between Aβ production from an amyloid precursor protein and its removal from the brain is the main cause of Aβ accumulation and its pathogenesis. Intra-neuronal Aβ aggreagates result in endolysosomal-autophagic dysfunctions followed by formation of authophagic vacuoles and damaged mitochondria in neurons. Studies have also shown that there is an intense crosstalk between Aβ and tau proteins. Aβ aggregates inside and outsides of neurons and intra-neuronal hyper-phosphorylated tau induce dendritic spines collapse and synaptic degeneration, which finally lead to memory loss in AD patients. The amyloid plaques at early stages of AD are detected in the neocortex and hippocampus which extended to the other brain areas associated with conversion from preclinical to symptomatic AD. Other pathologic factors, such as glia-mdiated inflammation and neuronal death, in AD lead to decrease in neuronal functions leading to cognitive impairments.
The better understanding of cellular and molecular mechanisms involved in AD and identifying sensitive and specific biomarkers can play main roles in early diagnosis, controlling the progression, and effective treatmnents of AD. In this study, we review the latest findings on pathophysiology of Aβ and tau proteins and their roles in pathogenesis of AD as well as their importance as targets for treatment of AD.