Alzheimer’s Disease Pathogenesis: Interactions Among Glial Cells, Inflammasomes, Caspases, and Signaling Pathways and Their Implications for Earlier Diagnosis

Alzheimer’s Disease (AD) is a progressive and irreversible neurodegenerative disorder that slowly destroys one’s memory and thinking skills and is traditionally associated with amyloid-beta (Aβ) accumulation and tau neurofibrillary tangle formation. However, these features alone do not fully explain disease progression. Increasing evidence shows that chronic neuroinflammation serves as a major contributor to neuronal damage, but the interactions among the inflammatory pathways remain incompletely understood. Rather than evaluating each mechanism independently, this literature review examines how neuroinflammation, glial cells, the PI3K/AKT pathway, inflammasomes, SHIP-1, caspases, and genes and biomarkers interact to promote AD pathogenesis and evaluates their role in AD progression, which can eventually lead to an evaluation of their potential as biomarkers and therapeutic targets. The evidence indicates that microglial and astrocytic activation promotes inflammatory mediators, such as interleukins and cytokines. NLRP3 and NLRP1 inflammasome activation enhances caspase activity, cytokine maturation, pyroptosis, and tau formation. Furthermore, the dysregulation of the PI3K/Akt signaling pathway causes tau formation and amyloid beta plaque formation. Caspases additionally contribute to apoptosis, synaptic dysfunction, protein cleavage, autophagy, and more, exacerbating AD pathogenesis and neuroinflammation. Dysregulation of the SHIP-1 signalling pathway alters microglial activity and chromosomal function and contributes to further neuroinflammation. Altogether, the findings of this review support AD’s pathogenesis as an interconnected inflammatory pathway rather than independent actors. Understanding these interactions aids in identifying earlier inflammatory biomarkers and developing targeted therapies to intervene before severe AD.