Common Signaling Pathways Involved in Alzheimer's Disease and Stroke: Two Faces of the Same Coin

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-β aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are the disruption of neuronal circuitry at different levels of cellular signaling, leading to the death of neurons and glial cells in the brain. Therefore, it is necessary to find out the common molecular mechanisms of these two diseases to understand their etiological connections. Here, we summarized the most common signaling cascades including autotoxicity, ApoE4, insulin signaling, inflammation, mTOR-autophagy, notch signaling, and microbiota-gut-brain axis, present in both AD and IS. These targeted signaling pathways reveal a better understanding of AD and IS and could provide a distinguished platform to develop improved therapeutics for these diseases.