title: Plasma phospholipids identify antecedent memory impairment in older adults.
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.
authors.affiliation: Department of Neurology, University of Rochester School of Medicine, Rochester, New York, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Mapstone
authors.affiliation: 1] Department of Oncology, Georgetown University Medical Center, Washington, DC, USA. [2] Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: 1] Department of Neurology, Georgetown University Medical Center, Washington, DC, USA. [2] Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Massimo S
authors.identifier: 0000000283761934
authors.initials: MS
authors.lastname: Fiandaca
authors.affiliation: Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Mhyre
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Linda H
authors.initials: LH
authors.lastname: MacArthur
authors.affiliation: Department of Medicine, University of Rochester School of Medicine, Rochester, New York, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hall
authors.affiliation: 1] Department of Public Health Sciences, University of Rochester School of Medicine, Rochester, New York, USA. [2].
authors.forename: Susan G
authors.initials: SG
authors.lastname: Fisher
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester School of Medicine, Rochester, New York, USA.
authors.forename: Derick R
authors.initials: DR
authors.lastname: Peterson
authors.affiliation: Department of Medicine, Unity Health System, Rochester, New York, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Haley
authors.affiliation: Department of Family Medicine, Unity Health System, Rochester, New York, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nazar
authors.affiliation: Division of Long Term Care and Senior Services, Rochester General Hospital, Rochester, New York, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rich
authors.affiliation: 1] Department of Neurobiology and Behavior, University of California, Irvine School of Medicine, Irvine, California, USA. [2].
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Berlau
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine School of Medicine, Irvine, California, USA.
authors.forename: Carrie B
authors.initials: CB
authors.lastname: Peltz
authors.affiliation: Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tan
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine School of Medicine, Irvine, California, USA.
authors.forename: Claudia H
authors.initials: CH
authors.lastname: Kawas
authors.affiliation: 1] Department of Neurology, Georgetown University Medical Center, Washington, DC, USA. [2] Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D001216:Asparagine / Q000097:blood; D015415:Biomarkers; D002331:Carnitine / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D015331:Cohort Studies; D004151:Dipeptides / Q000097:blood; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008244:Lysophosphatidylcholines / Q000097:blood; D008293:Malates / Q000097:blood; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D055442:Metabolome; D009483:Neuropsychological Tests; D010713:Phosphatidylcholines / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D010743:Phospholipids / Q000097:blood*; D011392:Proline / Q000097:blood; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013109:Sphingomyelins / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D008244:Lysophosphatidylcholines; D008293:Malates; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010743:Phospholipids; D013109:Sphingomyelins; C024033:glycoursodeoxycholic acid; D001216:Asparagine; D014580:Ursodeoxycholic Acid; C030298:malic acid; D011392:Proline; D002331:Carnitine