Analyte |
Volunteer |
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Matrix |
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Method |
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est Cost $ |
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Sources/Vendors/Comments (see text for volumes, cost, etc) |
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Feasible and Core Analytes |
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Tau (total, phospho) |
Hampel |
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CSF |
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ELISA |
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50 per |
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Innogenetics; Molecular Geriatrics Corporation; MIE University, Japan, Mitsubishi. Consider all phospho-taus; |
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Ab total, 1-42 |
Mehta |
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plasma, CSF |
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ELISA |
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50 per |
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Innogenetics (for Ab1-42 in CSF only, no other reliable kits) Consider all Ab, e.g., C-terminus-truncated; |
CRP |
Rogers |
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plasma, CSF |
ELISA |
|
40 |
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Vendors: Alerchek (Portland, ME), Alpha Diagnostic (San Antonio), American Diagnostica (Greenwich, CT), United Biotech (Mountain View, CA). CRP may be included in the standard laboratory analyses; see also CD59 in "uncertain feasibilty" category; |
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C1Q |
Rogers |
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plasma, CSF |
ELISA |
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30 |
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Vendors: ELISA kits can bemade from Quidel (La Jolla) antibodies. see CD59 in "uncertain feasibilty" category |
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IL-6/IL-6R |
Hampel |
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serum CSF |
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ELISA |
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75 |
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vendor=R&D Systems; consider also soluble glycoprotein 130 (sgp130); all contribute to assessment of phospho-tau despite potential for confounding as for other inflammatory markers |
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DNA, RNA |
Hardy |
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blood |
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genotyping |
400 |
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IC to allow "freedom to operate" IP; establish target participation rate; include immortalization of cell lines (hence cost); Central lab options include Indiana University and the Coryell Institute. |
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oxysterols |
Galasko |
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plasma, CSF |
GC/MS |
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100 |
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cross-sectional increase in CSF; requires also plasma cholesterol and 24-s-OH-cholesterol (see also Apo E); University of Bonn |
homocysteine |
Galasko |
|
plasma |
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ELISA |
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20 |
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homocysteine may be included in the standard laboratory analyses; numerous academic laboratories also can perform; measure also B12, folate, RBC folate in parallel (see standard clinical labs) |
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APP |
Galasko |
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CSF |
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ELISA |
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75 |
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total APP, s-APP-beta, s-APP-alpha. Vendor: not readily available; need to contact groups that have published data . Opportunity for "big PhRMA" to contribute in kind (Aby) |
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ApoE |
Mehta |
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DNA, plasma |
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40 |
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genotyping (cross-sectional) and phenotyping (both cross-sectional and longitudinal, perhaps also in CSF) |
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isoprostane |
Trojanowski |
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plasma CSF urine |
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GC/MS |
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50 |
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analysis can be done after reasonabl e shipping/storage, esp interesting for anti-oxidant mechanisms of drug action |
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alpha-antichymotrypsin |
Mehta |
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blood CSF |
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ELISA |
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? |
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Commercial kit from Boehringer-Ingelheim (nephelometry); Aby for ELISA commonly available but no commercial kit |
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Nitro-tyrosine |
Siemers |
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CSF |
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HPLC, ED |
40 |
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relevant to mechamnisms downstream from microglial activation |
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Analyte |
Volunteer |
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Matrix |
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Method |
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Sources/Vendors/References (see text for volumes, cost, etc) |
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Feasible Analytes, not core |
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Abeta antibodies |
Rogers |
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blood CSF |
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ELISA |
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no commercial kits but academic units available as central lab; may benefit from immortalization of cell lines (see DNA) |
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Glutamine synthetase |
Galasko |
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serum, CSF |
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ELISA |
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vendor SYN-X pharma, Canada |
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GFAP |
Mehta |
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CSF |
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ELISA |
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no kit |
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sulfatide |
Siemers |
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CSF |
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MS |
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vendor=Linco, Inc ("lipid-omics") |
AD7C (NTP) |
Galasko |
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CSF, plama |
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neurodegeneration marker should track with tau; vendor=Nymox, Canada |
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Analytes of uncertain feasibility for multi-center clinical trials |
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Ab 1-40 |
Mehta |
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blood, CSF |
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ELISA |
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Consider all Ab, e.g., C-terminus-truncated; academic labs or potential future kit or PhRMA development (Takeda?) |
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CD59 |
Rogers |
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blood, CSF |
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ELISA |
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easily confounded by intercurrent infection, requires medical history at each collection; consider multiple collections over days/weeks and use lowest value to minimize confounding effect of other inflammatory processes |
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melanotransferrin (p97) |
Galasko |
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serum, CSF |
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immunoblot |
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cross-sectional increase in AD; vendor: antibody from ATCC, Rockville, MD; may be confounded in plasma by limited crossing of BBB, and altermative sources in the periphery |
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APP platelet ratio |
Galasko |
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platelets from 27 mL blood |
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immunoblot, densitometric |
commercially available antibody (22C11) |
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Synaptic markers |
Galasko |
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CSF |
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immunoblot |
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e.g., synaptophysin, synaptotagmin; no vendors |
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S100B |
Mehta |
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blood, CSF |
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ELISA |
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conflicting reports, results not reproducible |
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Neurofilaments, phospho |
Galasko |
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CSF |
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ELISA |
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antibodies are commercially available; assays by Hu, Iqbal, Rosengren |
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a - synuclein |
Trojanowski |
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CSF |
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ELISA |
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Molecular chaperones |
Trojanowski |
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CSF |
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e.g., Ubiquitin |
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8-OH-guanidine |
Siemers |
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CSF, plasma, urine |
HPLC, GC/MS |
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