title: Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease.
abstract: Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ-, and amyloid (A) β42-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitive impairment (MCI), Alzheimer disease (AD) dementia, or Parkinson disease. APOE ε4/ε4 participants had CSF apoE-positive particles that were more frequently larger but at an 88% lower level versus those in APOE ε3/ε3 or APOE ε3/ε4 patients; this finding was reproduced in conditioned medium from mouse primary glial cell cultures with targeted replacement of apoE. Cerebrospinal fluid apoE-positive and β-amyloid (Aβ42)-positive particle concentrations were persistently reduced one-third to one-half in middle and older age subjects; apoAI-positive particle concentration progressively increased approximately 2-fold with age. Both apoAI-positive and annexin V-positive CSF particle levels were reduced one-third to one-half in CSF of MCI and/or AD dementia patients versus age-matched controls. Our approach provides new methods to investigate CNS lipid biology in relation to neurodegeneration and perhaps develop new biomarkers for diagnosis or treatment monitoring.
authors.affiliation: From the Department of Pathology, University of Washington, Seattle, WA (YY, CDK, EC, AMW, KSM, JZ, GSB, TJM); Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA; (ERP, GL); VA Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA (ERP); Department of Neurosciences, University of California San Diego, La Jolla, CA (DRG); Department of Neurology, University of Washington, Seattle, WA (S-CH); Department of Medicine, University of Washington, Seattle, WA (C-EY); Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA (C-EY); Department of Laboratory Medicine, University of Washington, Seattle, WA (GSB); and Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (BTH).
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hu
authors.forename: Eiron
authors.initials: E
authors.lastname: Cudaback
authors.forename: Angela M
authors.initials: AM
authors.lastname: Wilson
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Montine
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Baird
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000235:genetics; D055354:Exosomes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000134:cerebrospinal fluid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008055:Lipids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins