title: Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease.
abstract: The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer's disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-β1-42 (Aβ1-42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, Aβ1-42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both Aβ and tau pathologies in a restricted subgroup of AD patients.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314-6399, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chalbot
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000503:physiopathology; D016824:Antigens, Human Platelet / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D016824:Antigens, Human Platelet; D015415:Biomarkers; C083451:human platelet antigen 1b