The Role of Amyloid-Beta Plaques in Disrupting Neural Communication in Alzheimer’s Disease

Alzheimer’s Disease (AD) is defined as a particular onset and course of cognitive and functional decline. Central to AD pathology is the abnormal processing of amyloid precursor proteins (APPs), which produces amyloid-beta (Aβ) peptides prone to misfolding and aggregation. Soluble Aβ oligomers are now also recognized as the earliest and most potent disruptors of synaptic communication, leading to the impairment of receptor function and long-term potentiation. These amyloidogenic events serve as an upstream trigger for the hyperphosphorylation and aggregation of tau. As Aβ accumulation progresses, it activates kinases that drive tau hyperphosphorylation, misfolding, and neurofibrillary tangle formation. These effects destabilize microtubules and interrupt axonal transport. The combined effect of Aβ-induced synaptic toxicity, tau-mediated structural breakdown, and chronic neuroinflammation leads to the progressive loss of neural connectivity characteristic of Alzheimer’s Disease. This paper will examine how Aβ plaques create disruptions in neural signaling, enabling the transition of tau from a microtubule-stabilizing protein to a neurotoxic aggregate. By evaluating Aβ as the initiator of synaptic stress and tau as the primary driver for structural neurodegeneration and clinical decline, this review aims to show that the loss of neural connectivity in AD is the result of this interdependent proteinopathy, which is further exaggerated by chronic neuroinflammation.