Involvement and Mechanisms of Aβ and Tau in the NeuroinflammatoryResponse of Alzheimer’s Disease

Alzheimer's disease (AD) is a common chronic neurodegenerative disorder, serving as the most prevalent cause of dementia among the elderly. The primary histopathological hallmarks of AD encompass senile plaques, induced by excessive deposition of extracellular β-amyloid (Aβ), and neurofibrillary tangles (NFT), resulting from excessive phosphorylation of intracellular Tau protein, leading to neuronal damage and loss. Numerous studies on AD patients and animal models have revealed the widespread presence of neuroinflammatory responses within the AD brain, emphasizing the pivotal role of neuroinflammation in the pathogenesis of AD, which is now widely recognized as one of the primary triggers of AD. Microglia, the resident macrophages in the brain and the first line of defense of the central nervous system, play a central role in neuroinflammation. In the pathogenesis of AD, microglia are considered a double-edged sword, exerting beneficial effects by clearing Aβ deposition while causing detrimental effects through the production of cytotoxic substances, leading to neuronal dysfunction. Although the precise role of neuroinflammation in the pathogenesis of AD remains incompletely elucidated, an increasing number of studies have revealed that pathological Aβ and Tau proteins are extensively involved in the neuroinflammatory process mediated by microglia activation in AD, exhibiting a complex interplay. Therefore, this article will provide a comprehensive review of the research progress on the relationship between Aβ or Tau proteins and neuroinflammation induced by microglia in AD, as well as its associated mechanisms.