This study investigates the use of plasma phospholipids as biomarkers to identify preclinical Alzheimer's disease in older adults. The researchers enrolled 525 participants aged 70 and older who were otherwise healthy and followed them for up to 5 years. Over the course of the study, 74 participants met criteria for amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD). The study identified a set of ten lipids in peripheral blood that predicted phenoconversion to either aMCI or AD within a 2-3 year timeframe with over 90% accuracy. These lipids, which reflect cell membrane integrity, were found to be depleted in participants who later developed cognitive impairment. The biomarker panel was validated using an independent sample set, demonstrating high sensitivity and specificity for classifying cognitively normal individuals who would progress to aMCI or AD. This study provides a promising blood-based biomarker panel for detecting preclinical Alzheimer's disease, which could be useful for early intervention and prevention strategies.This study investigates the use of plasma phospholipids as biomarkers to identify preclinical Alzheimer's disease in older adults. The researchers enrolled 525 participants aged 70 and older who were otherwise healthy and followed them for up to 5 years. Over the course of the study, 74 participants met criteria for amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD). The study identified a set of ten lipids in peripheral blood that predicted phenoconversion to either aMCI or AD within a 2-3 year timeframe with over 90% accuracy. These lipids, which reflect cell membrane integrity, were found to be depleted in participants who later developed cognitive impairment. The biomarker panel was validated using an independent sample set, demonstrating high sensitivity and specificity for classifying cognitively normal individuals who would progress to aMCI or AD. This study provides a promising blood-based biomarker panel for detecting preclinical Alzheimer's disease, which could be useful for early intervention and prevention strategies.