A-beta Signaling Pathways

Alzheimer’s disease (AD) is a complex, neurodegenerative disorder that is characterized by neuroinflammation, neuronal cell death, the accumulation of amyloid plaques and neurofibrillary tangles (NFTs), and cortical and hippocampal atrophy. A key trigger of AD is believed to be the beta-Amyloid protein (A-beta), which is formed by the sequential enzymatic processing of Amyloid Precursor Protein (APP) by beta- and gamma-secretases. A-beta released into the extracellular space can aggregate to form oligomers, protofibrils, fibrils, and senile plaques. Soluble A-beta oligomers have been shown to be toxic to neuronal synapses. However, the molecular mechanisms underlying its cytotoxic effects appear to be very complex. A-beta oligomers interact with several putative receptors at excitatory synapses, stimulating intracellular signaling pathways that culminate in the inhibition of long-term potentiation (LTP), facilitation of long-term depression (LTD), and synapse loss. Additionally, A-beta oligomers can activate caspases, causing neuronal cell death, and induce cleavage and hyperphosphorylation of Tau, leading to the formation of NFTs.

To learn more A-beta, please visit our APP Cleavage and Amyloid-beta Degradation Research Area.