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Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity is increased in Alzheimer disease.

Artikel i vetenskaplig tidskrift
Författare Sonia Chalbot
Henrik Zetterberg
Kaj Blennow
Tormod Fladby
Inge Grundke-Iqbal
Khalid Iqbal
Publicerad i Clinical chemistry
Volym 55
Nummer/häfte 12
Sidor 2171-9
ISSN 1530-8561
Publiceringsår 2009
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 2171-9
Språk en
Länkar dx.doi.org/10.1373/clinchem.2009.13...
Ämnesord Adult, Aged, Alzheimer Disease, cerebrospinal fluid, enzymology, Biological Markers, cerebrospinal fluid, Calcium, physiology, Fluorescent Dyes, Humans, Middle Aged, Phosphatidylcholines, Phospholipases A2, Secretory, cerebrospinal fluid, Reference Values, Young Adult
Ämneskategorier Psykiatri

Sammanfattning

BACKGROUND: The phospholipase A(2) (PLA2) family comprises multiple isoenzymes that vary in their physicochemical properties, cellular localizations, calcium sensitivities, and substrate specificities. Despite these differences, PLA2s share the ability to catalyze the synthesis of the precursors of the proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings, we developed a PLA2 assay and determined the predominant types of PLA2 activity in cerebrospinal fluid (CSF). METHODS: We used liposomes composed of a fluorescent probe (bis-Bodipy FL C11-PC [1,2-bis-(4,4- difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l-alpha-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96-well microtiter plate format. We established the type of CSF PLA2 activity using type-specific inhibitors of PLA2. RESULTS: Using 5 microL CSF per assay, our PLA2 activity assay was reproducible with CVs <15% in 2 CSF samples and for recombinant secretory Ca(2+)-dependent PLA2 (sPLA2) in concentrations ranging from 0.25 to 1 micromol/L. This PLA2 assay allowed identification of sPLA2 activity in lumbar CSF from healthy individuals 20-77 years old that did not depend on either sex or age. Additionally, CSF sPLA2 activity was found to be increased (P = 0.0008) in patients with Alzheimer disease. CONCLUSIONS: Adult human CSF has sPLA2 activity that can be measured reliably with the assay described. This enzyme activity in the CSF is independent of both sex and age and might serve as a valuable biomarker of neuroinflammation, as we demonstrated in Alzheimer disease.

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