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Novel Techniques for early detection of Alzheimer’s disease. Nicole Sassounian Joshue Leyva.
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Novel Techniques for early detection of Alzheimer’s disease Nicole Sassounian JoshueLeyva
Plasma phospholipids identify antecedent memory impairment in older adultsMark Mapstone, Amrita K Cheema, Massimo S Fiandaca, XiaogangZhong, Timothy R Mhyre, Linda H MacArthur, William J Hall, Susan G Fisher, Derick R Peterson, James M Haley, Michael D Nazar, Steven A Rich, Dan J Berlau, Carrie B Peltz, Ming T Tan, Claudia H Kawas& Howard J Federoff
Objective • To provide evidence for the use of blood-based biomarkers to detect preclinical Alzheimer’s disease (AD)
Study Methodology • 525 community-dwelling participants • Ages 70 or older • 5-year observational study
Study Methodology • 3 groups • Normal Control • aMCI/AD • Converter Phenoconversion
Phenoconversion • Individuals who converted to either amnestic MCI or mild AD • Composite measure of memory performance
Metabolite Identification • Method 1: untargeted analysis via LASSO • Revealed • lower phosphatidylinositol in the pre-converter group • higher glycoursodeoxycholic acid in the aMCI/AD group compared to the NC group
Metabolites • Method 2: targeted analysis via SID-MRM-MS • Revealed: • lower plasma levels of serotonin, phenylalanine, proline, lysine, phosphatidylcholine (PC), taurine and acylcarnitine (AC) in pre-converter participants who later phenoconverted to aMCI/AD
Depletion the plasma of the pre-converters but not in the control group • Metabolites remained depleted after phenoconversion to aMCI/AD (post-converters) and were similar to the levels in the aMCI/AD group
Results • Validated plasma metabolite changes that distinguish normal from AD adults • Metabolic panel accuracy: >90% • Detects phenoconversion from normal to aMCI/AD within 2-3 years (average)
Relevant? • Metabolites represent PCs and ACs • Role in function and structure of cell membranes • Plasma membrane deficits in AD patients • AD patients have decreased [PC] in plasma • Amyloid-beta disrupts bilayer integrity • Blood-based biomarkers • Easier, cheaper, faster