Brain-Derived Neurotrophic Factor (BDNF) is a key molecule involved in learning and memory, with its expression highly regulated and varying among individuals. BDNF levels are associated with both normal and pathological aging, as well as psychiatric diseases, particularly in brain regions critical for memory, such as the hippocampus and parahippocampal areas. Interventions like exercise and antidepressants can enhance BDNF expression in both healthy and pathological conditions. This review discusses studies on BDNF expression regulation, changes in the pathological brain, and the clinical relevance of interventions that enhance BDNF. While BDNF may not be a valid biomarker for neurodegenerative or neuropsychiatric diseases due to its common deregulation, it could serve as a marker for mnemonic symptoms common in many conditions. BDNF is a neurotrophin crucial for neuronal survival and differentiation during development and maintains high expression in the adult brain, regulating synaptic transmission and plasticity. Its expression is regulated at multiple levels, including transcription, translation, and post-translational modifications. BDNF has four promoters in rats, each driving different mRNA splicing patterns. BDNF is synthesized as proBDNF, which can be cleaved to produce mature BDNF. ProBDNF and mature BDNF have opposing effects on cellular function, with proBDNF binding to p75 NTR and inducing apoptosis, while mature BDNF binds to TrkB and promotes cell survival. BDNF is critical for synaptic plasticity and memory formation, promoting synaptic consolidation and spine complexity. It also increases neurogenesis through changes in cell survival and proliferation. BDNF is involved in various cognitive functions, including spatial and recognition memory. The Val66Met polymorphism in the BDNF gene affects synaptic targeting and activity-dependent release of BDNF, with Met carriers showing impaired synaptic plasticity and memory performance. Aging is associated with reduced BDNF levels, leading to synaptic plasticity deficits and cognitive impairments. BDNF levels decrease in the hippocampus and other brain regions, contributing to age-related memory decline. However, some studies show no change or even increased BDNF levels with aging, suggesting that hippocampal BDNF loss may not be a primary mechanism of age-related cognitive decline. BDNF plays a role in neuroprotection and memory consolidation, and its administration can prevent pathological changes in the nervous system associated with aging. In Alzheimer's disease, reduced BDNF levels are associated with cognitive deficits, and BDNF may contribute to the pathogenesis of the disease by modulating Aβ-induced toxicity. BDNF can protect against Aβ-mediated toxicity by contributing to its degradation and preventing tau hyperphosphorylation. BDNF dysregulation may contribute to synaptic dysfunction and mnemonic impairment in AD. BDNF levels are also linked to cognitive decline in mild cognitive impairment (MCI) and may be an earlyBrain-Derived Neurotrophic Factor (BDNF) is a key molecule involved in learning and memory, with its expression highly regulated and varying among individuals. BDNF levels are associated with both normal and pathological aging, as well as psychiatric diseases, particularly in brain regions critical for memory, such as the hippocampus and parahippocampal areas. Interventions like exercise and antidepressants can enhance BDNF expression in both healthy and pathological conditions. This review discusses studies on BDNF expression regulation, changes in the pathological brain, and the clinical relevance of interventions that enhance BDNF. While BDNF may not be a valid biomarker for neurodegenerative or neuropsychiatric diseases due to its common deregulation, it could serve as a marker for mnemonic symptoms common in many conditions. BDNF is a neurotrophin crucial for neuronal survival and differentiation during development and maintains high expression in the adult brain, regulating synaptic transmission and plasticity. Its expression is regulated at multiple levels, including transcription, translation, and post-translational modifications. BDNF has four promoters in rats, each driving different mRNA splicing patterns. BDNF is synthesized as proBDNF, which can be cleaved to produce mature BDNF. ProBDNF and mature BDNF have opposing effects on cellular function, with proBDNF binding to p75 NTR and inducing apoptosis, while mature BDNF binds to TrkB and promotes cell survival. BDNF is critical for synaptic plasticity and memory formation, promoting synaptic consolidation and spine complexity. It also increases neurogenesis through changes in cell survival and proliferation. BDNF is involved in various cognitive functions, including spatial and recognition memory. The Val66Met polymorphism in the BDNF gene affects synaptic targeting and activity-dependent release of BDNF, with Met carriers showing impaired synaptic plasticity and memory performance. Aging is associated with reduced BDNF levels, leading to synaptic plasticity deficits and cognitive impairments. BDNF levels decrease in the hippocampus and other brain regions, contributing to age-related memory decline. However, some studies show no change or even increased BDNF levels with aging, suggesting that hippocampal BDNF loss may not be a primary mechanism of age-related cognitive decline. BDNF plays a role in neuroprotection and memory consolidation, and its administration can prevent pathological changes in the nervous system associated with aging. In Alzheimer's disease, reduced BDNF levels are associated with cognitive deficits, and BDNF may contribute to the pathogenesis of the disease by modulating Aβ-induced toxicity. BDNF can protect against Aβ-mediated toxicity by contributing to its degradation and preventing tau hyperphosphorylation. BDNF dysregulation may contribute to synaptic dysfunction and mnemonic impairment in AD. BDNF levels are also linked to cognitive decline in mild cognitive impairment (MCI) and may be an early