The pathogenesis of Alzheimer’s disease involves several interconnected mechanisms that contribute to neuronal dysfunction and brain atrophy. One of the central features of AD is the accumulation of amyloid-beta (Aβ) plaques in the brain. The resultant Aβ peptides aggregate to form insoluble plaques that disrupt cell-to-cell communication and activate immune responses, leading to inflammation and neuronal damage. Another hallmark of Alzheimer’s disease is the presence of neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Normally, tau stabilizes microtubules in neurons, which are essential for intracellular transport. In AD, abnormal phosphorylation of tau causes it to detach from microtubules and aggregate into tangles. This process impairs the microtubule network, disrupting axonal transport and leading to neuronal cell death. Neuroinflammation also plays a significant role in Alzheimer’s disease pathogenesis. Chronic activation of microglia leads to the release of pro-inflammatory cytokines and chemokines, which can exacerbate neuronal injury and promote further tau pathology.Oxidative stress is another contributing factor in Alzheimer’s disease. This oxidative stress is often linked to mitochondrial dysfunction, which further impairs cellular energy metabolism and contributes to neuronal death. Additionally, genetic factors play a role in the development of Alzheimer’s disease. Alzheimer’s disease pathogenesis involves a multifaceted interplay of amyloid-beta accumulation, tau pathology, neuroinflammation, oxidative stress, synaptic dysfunction, and genetic predispositions. Understanding these mechanisms is crucial for developing targeted therapies to slow or halt the progression of this devastating disease. This chapter focuses on the molecular mechanisms underlying neuronal damage in Alzheimer’s disease. It offers an in-depth examination of the pathological changes that occur in the brain, such as the accumulation of amyloid beta plaques and the formation of tau protein tangles. These accumulations disrupt cell function and are considered key indicators of Alzheimer’s disease. The text delves into how amyloid-beta peptides aggregate to form plaques outside neurons, interfering with cell-to-cell communication.