The article by Mark P. Mattson discusses the progressive neurodegenerative process of Alzheimer's disease (AD), focusing on the molecular and cellular alterations that lead to synaptic dysfunction and neuronal death. AD is a neurodegenerative disorder affecting nearly 2% of the population in industrialized countries, with a significant increase in risk for those over 70 years old. The disease is characterized by the presence of "plaques" and "tangles" in the brain, primarily in regions involved in learning, memory, and emotional behaviors. These alterations are due to the progressive dysfunction and death of nerve cells, which are responsible for information storage and processing. The article highlights the role of the amyloid precursor protein (APP) in the production of amyloid β-peptide (Aβ), which forms the plaques. Mutations in APP, presenilin-1 (PS1), and presenilin-2 (PS2) genes lead to increased Aβ production and aggregation, contributing to neuronal degeneration. Genetic and environmental factors, such as apolipoprotein E (ApoE) isoforms and dietary components like folate and cholesterol, influence the risk of AD. Key cellular stressors in AD include oxidative stress, impaired energy metabolism, and perturbed calcium homeostasis. Aβ is particularly toxic when it forms soluble oligomers, impairing synaptic function and leading to neuronal death. The article also discusses the involvement of glial cells, such as astrocytes, oligodendrocytes, and microglia, in the neurodegenerative process. Finally, the article explores potential pathways for preventing and treating AD, including dietary and lifestyle modifications, targeted therapeutics, and immune-based approaches. These include cognitive stimulation, physical exercise, dietary restrictions, and drugs that target specific sites in the neurodegenerative cascade, such as β- and γ-secretase inhibitors. The development of effective interventions is an area of active research, with promising results from animal models and initial clinical trials.The article by Mark P. Mattson discusses the progressive neurodegenerative process of Alzheimer's disease (AD), focusing on the molecular and cellular alterations that lead to synaptic dysfunction and neuronal death. AD is a neurodegenerative disorder affecting nearly 2% of the population in industrialized countries, with a significant increase in risk for those over 70 years old. The disease is characterized by the presence of "plaques" and "tangles" in the brain, primarily in regions involved in learning, memory, and emotional behaviors. These alterations are due to the progressive dysfunction and death of nerve cells, which are responsible for information storage and processing. The article highlights the role of the amyloid precursor protein (APP) in the production of amyloid β-peptide (Aβ), which forms the plaques. Mutations in APP, presenilin-1 (PS1), and presenilin-2 (PS2) genes lead to increased Aβ production and aggregation, contributing to neuronal degeneration. Genetic and environmental factors, such as apolipoprotein E (ApoE) isoforms and dietary components like folate and cholesterol, influence the risk of AD. Key cellular stressors in AD include oxidative stress, impaired energy metabolism, and perturbed calcium homeostasis. Aβ is particularly toxic when it forms soluble oligomers, impairing synaptic function and leading to neuronal death. The article also discusses the involvement of glial cells, such as astrocytes, oligodendrocytes, and microglia, in the neurodegenerative process. Finally, the article explores potential pathways for preventing and treating AD, including dietary and lifestyle modifications, targeted therapeutics, and immune-based approaches. These include cognitive stimulation, physical exercise, dietary restrictions, and drugs that target specific sites in the neurodegenerative cascade, such as β- and γ-secretase inhibitors. The development of effective interventions is an area of active research, with promising results from animal models and initial clinical trials.