Alzheimer's disease (AD) is a progressive and complicated neurological illness that is the most common cause of dementia worldwide. Despite extensive research, the pathophysiological causes of Alzheimer's Disease (AD) remain inadequately understood, and no cures currently exist. This review summarizes recent advancements in our understanding of AD pathogenesis, concentrating on molecular, cellular, and systemic mechanisms. Significant findings indicate that emerging insights into amyloid-beta (Aβ) fibril polymorphisms, nanoplaques, and clearance deficiencies are altering the paradigm, despite the amyloid cascade hypothesis continuing to inform the initial stages of the disease.It is now known that tau pathology is a dynamic process that acts like a prion and is affected by glial contacts and changes after translation. Chronic neuroinflammation makes neural injuries worse. This is caused by glial senescence, astrocytic GABA signaling, and NLRP3 inflammasome activation.Oxidative stress, mitophagy impairment, and mitochondrial dysfunction are some of the things that can lead to dementia. Loss of synapses, which is closely linked to cognitive impairment, happens when neurotransmission is disrupted and microglial pruning is done incorrectly.Pathological cascades are exacerbated by vascular and metabolic dysfunctions, including insulin resistance, glymphatic failure, and pericyte depletion. Neurogranin, CSF MTBR-tau243, plasma p-tau217, and AI-based neuroimaging metrics exemplify novel diagnostic biomarkers that are improving early detection. Antioxidants, senolytics, epigenetic therapies, and gut-brain axis regulation represent therapeutic advancements that extend beyond the targeting of Aβ and tau. All of these results show how complicated AD is and support using more than one method to improve diagnosis, treatment, and long-term outcomes.
