학술논문

Plasma phospholipids identify antecedent memory impairment in older adults.
Document Type
article
Source
Nature medicine. 20(4)
Subject
Humans
Alzheimer Disease
Memory Disorders
Malates
Ursodeoxycholic Acid
Sphingomyelins
Phospholipids
Phosphatidylcholines
Phosphatidylinositols
Lysophosphatidylcholines
Carnitine
Asparagine
Proline
Dipeptides
Sensitivity and Specificity
Cohort Studies
Longitudinal Studies
Prospective Studies
Neuropsychological Tests
Aged
Female
Male
Metabolome
Biomarkers
Cognitive Dysfunction
Immunology
Medical and Health Sciences
Language
Abstract
Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.