This review explores the molecular mechanisms linking osteoarthritis (OA) and Alzheimer's Disease (AD), highlighting shared pathways, mechanisms, and potential therapeutic prospects. AD is a progressive neurodegenerative disorder characterized by cognitive decline due to impaired neurotransmission and neuronal death, primarily affecting the elderly. Key pathological hallmarks include amyloid beta (Aβ) peptide deposition and hyperphosphorylated tau protein aggregation. OA, a common joint disease, involves progressive cartilage degeneration and synovitis, often affecting weight-bearing joints like the knees, spine, and hips. Both conditions are influenced by genetic and environmental factors, including low-grade systemic inflammation, which may contribute to the development and progression of AD. The review discusses the role of systemic inflammation in AD pathogenesis, emphasizing how it can disrupt the blood-brain barrier (BBB) and enhance neuroinflammation. Peripheral inflammation, particularly from conditions like obesity, hypertension, and diabetes, is linked to AD through shared inflammatory pathways. Genetic factors, such as APOE ε4, TREM2, and CD33, also play crucial roles in both AD and OA. The interplay between OA and AD is further explored through animal models and epidemiological studies, which suggest that OA can exacerbate AD pathology by increasing neuroinflammation and Aβ deposition. Common miRNAs, such as miR-9, 16, 29a, 124, and 132, are dysregulated in both conditions, potentially contributing to their shared pathogenesis. Therapeutic strategies targeting common pathways between OA and AD are discussed, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), disease-modifying osteoarthritis drugs (DMOADs), statins, and glucocorticoids. These treatments may have neuroprotective effects and could potentially prevent or slow the progression of both conditions. Precision medicine, which tailors interventions to individual genetic and metabolic profiles, is highlighted as a promising approach to address the shared paths between OA and AD. The review concludes by emphasizing the need for further research to fully understand the complex interplay between OA and AD and to develop effective prevention and treatment strategies.This review explores the molecular mechanisms linking osteoarthritis (OA) and Alzheimer's Disease (AD), highlighting shared pathways, mechanisms, and potential therapeutic prospects. AD is a progressive neurodegenerative disorder characterized by cognitive decline due to impaired neurotransmission and neuronal death, primarily affecting the elderly. Key pathological hallmarks include amyloid beta (Aβ) peptide deposition and hyperphosphorylated tau protein aggregation. OA, a common joint disease, involves progressive cartilage degeneration and synovitis, often affecting weight-bearing joints like the knees, spine, and hips. Both conditions are influenced by genetic and environmental factors, including low-grade systemic inflammation, which may contribute to the development and progression of AD. The review discusses the role of systemic inflammation in AD pathogenesis, emphasizing how it can disrupt the blood-brain barrier (BBB) and enhance neuroinflammation. Peripheral inflammation, particularly from conditions like obesity, hypertension, and diabetes, is linked to AD through shared inflammatory pathways. Genetic factors, such as APOE ε4, TREM2, and CD33, also play crucial roles in both AD and OA. The interplay between OA and AD is further explored through animal models and epidemiological studies, which suggest that OA can exacerbate AD pathology by increasing neuroinflammation and Aβ deposition. Common miRNAs, such as miR-9, 16, 29a, 124, and 132, are dysregulated in both conditions, potentially contributing to their shared pathogenesis. Therapeutic strategies targeting common pathways between OA and AD are discussed, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), disease-modifying osteoarthritis drugs (DMOADs), statins, and glucocorticoids. These treatments may have neuroprotective effects and could potentially prevent or slow the progression of both conditions. Precision medicine, which tailors interventions to individual genetic and metabolic profiles, is highlighted as a promising approach to address the shared paths between OA and AD. The review concludes by emphasizing the need for further research to fully understand the complex interplay between OA and AD and to develop effective prevention and treatment strategies.