Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by extracellular β-amyloid (Aβ) plaques and intracellular hyperphosphorylated tau (pTau) neurofibrillary tangles. AD is associated with memory deterioration and various cognitive and behavioral impairments. While the exact molecular mechanisms of AD are not fully understood, APOE variants, infections, and inflammation are significant risk factors. Aβ and pTau accumulation play critical roles in AD neurodegeneration. Experimental models, diagnostic strategies, and peripheral biomarkers are being developed for early detection and treatment. Recent advances include Aβ-targeted drugs and novel strategies for pTau targeting. Current challenges include the lack of animal models that accurately replicate AD pathologies. APOE4 is a major genetic risk factor for AD, increasing the risk of both early- and late-onset AD. APOE4 promotes Aβ aggregation and impairs Aβ clearance, contributing to AD pathology. APOE4 also affects tau pathology by promoting tau phosphorylation and aggregation. Microbial infections, such as herpesviruses, HCV, and bacteria like H. pylori and P. gingivalis, are associated with AD. Gut microbiota and neuroinflammation also play roles in AD. Glial cells, including microglia and astrocytes, are involved in Aβ clearance and neuroinflammation. Aβ generation and degradation are regulated by various pathways, including the amyloidogenic and non-amyloidogenic pathways. Aβ overproduction and aggregation are influenced by gene mutations, post-translational modifications, and environmental factors. Understanding these mechanisms is crucial for developing effective therapies for AD.Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by extracellular β-amyloid (Aβ) plaques and intracellular hyperphosphorylated tau (pTau) neurofibrillary tangles. AD is associated with memory deterioration and various cognitive and behavioral impairments. While the exact molecular mechanisms of AD are not fully understood, APOE variants, infections, and inflammation are significant risk factors. Aβ and pTau accumulation play critical roles in AD neurodegeneration. Experimental models, diagnostic strategies, and peripheral biomarkers are being developed for early detection and treatment. Recent advances include Aβ-targeted drugs and novel strategies for pTau targeting. Current challenges include the lack of animal models that accurately replicate AD pathologies. APOE4 is a major genetic risk factor for AD, increasing the risk of both early- and late-onset AD. APOE4 promotes Aβ aggregation and impairs Aβ clearance, contributing to AD pathology. APOE4 also affects tau pathology by promoting tau phosphorylation and aggregation. Microbial infections, such as herpesviruses, HCV, and bacteria like H. pylori and P. gingivalis, are associated with AD. Gut microbiota and neuroinflammation also play roles in AD. Glial cells, including microglia and astrocytes, are involved in Aβ clearance and neuroinflammation. Aβ generation and degradation are regulated by various pathways, including the amyloidogenic and non-amyloidogenic pathways. Aβ overproduction and aggregation are influenced by gene mutations, post-translational modifications, and environmental factors. Understanding these mechanisms is crucial for developing effective therapies for AD.