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Topic: Neurodegenerative Diseases Title: Lipid Metabolism Disruptions as Early Noninvasive Biomarkers of Alzheimer’s Disease: A Lipidomics Review Objective: To analyze how disruptions in lipid metabolism and cholesterol processing, which include changes in the levels of sphingolipids, ceramides, plasmalogens, and cholesteryl esters, help in early detection of Alzheimer’s disease, and to analyze whether these lipid alterations are reliable, noninvasive biomarkers for diagnosis and disease progression. Background: Alzheimer’s disease is increasingly linked to early disruptions in how the brain processes lipids and energy. Studies in metabolomics and lipidomics show that individuals with Alzheimer's often experience shifts in cholesterol-related lipids, fatty acids, and other metabolic pathways before noticeable symptoms develop. Because these changes can be detected in blood or cerebrospinal fluid, they raise the possibility of identifying the disease much earlier. However, lipid patterns widely vary between individuals, and the complexity of measuring so many lipids makes it difficult to determine which markers are the most reliable predictors of disease and age. Methods: To investigate whether cholesterol-related lipid biomarkers can aid in early diagnosis of Alzheimer’s and Parkinson’s disease, we conducted a structured literature review using Web of Science. We screened studies focused on lipidomics, metabolomics, and cholesterol-transport pathways. Articles analyzing blood, cerebrospinal fluid, and post-mortem brain tissue were included in the analysis. Across studies, we compared reported alterations in sphingolipids, ceramides, plasmalogens, cholesteryl esters, desmosterol, and ApoE/ABCA1 activity. We synthesized findings to evaluate which lipid signatures most consistently distinguished early neurodegeneration and predicted disease progression. Results: A total of 141 articles were extracted from Web of Science using targeted keywords, revealing that altered lipid metabolism and cholesterol transport are early indicators of Alzheimer's and Parkinson's disease. It was primarily identified using lipidomic, metabolic and multi-omics profiling. Findings included decreased sphingomyelins, cholesterol esters, desmosterol, plasmalogens, increased ceramides, and altered ApoE and ABCA1 activity Conclusions: Biomarkers of lipid metabolism and cholesterol transport are sufficient methods of indicating onset Alzheimer’s and Parkinson’s disease. Despite this method not being wildly used due to not being a conformities method, we can further use biomarkers to eventually benefit early diagnosis.