Analyte | Volunteer | | Matrix | | Method | | est Cost $ | | Sources/Vendors/Comments (see text for volumes, cost, etc) |
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Feasible and Core Analytes | | | | | | | | |
Tau (total, phospho) | Hampel | | CSF | | ELISA | | 50 per | | Innogenetics; Molecular Geriatrics Corporation; MIE University, Japan, Mitsubishi. Consider all phospho-taus; |
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Ab total, 1-42 | Mehta | | plasma, CSF | | ELISA | | 50 per | | Innogenetics (for Ab1-42 in CSF only, no other reliable kits) Consider all Ab, e.g., C-terminus-truncated; |
CRP | Rogers | | plasma, CSF | ELISA | | 40 | | 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 | | plasma, CSF | ELISA | | 30 | | 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 | | serum CSF | | ELISA | | 75 | | 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 | | blood | | genotyping | 400 | | 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 | | plasma, CSF | GC/MS | | 100 | | cross-sectional increase in CSF; requires also plasma cholesterol and 24-s-OH-cholesterol (see also Apo E); University of Bonn |
homocysteine | Galasko | | plasma | | ELISA | | 20 | | 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 | | CSF | | ELISA | | 75 | | 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 | | DNA, plasma | | | | 40 | | genotyping (cross-sectional) and phenotyping (both cross-sectional and longitudinal, perhaps also in CSF) |
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isoprostane | Trojanowski | | plasma CSF urine | | GC/MS | | 50 | | 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 | | blood CSF | | ELISA | | ? | | Commercial kit from Boehringer-Ingelheim (nephelometry); Aby for ELISA commonly available but no commercial kit |
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Nitro-tyrosine | Siemers | | CSF | | HPLC, ED | 40 | | relevant to mechamnisms downstream from microglial activation |
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Analyte | Volunteer | | Matrix | | Method | | | | Sources/Vendors/References (see text for volumes, cost, etc) |
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Feasible Analytes, not core | | | | | | | | |
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Abeta antibodies | Rogers | | blood CSF | | ELISA | | | | 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 | | serum, CSF | | ELISA | | | | vendor SYN-X pharma, Canada |
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GFAP | Mehta | | CSF | | ELISA | | | | no kit |
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sulfatide | Siemers | | CSF | | MS | | | | vendor=Linco, Inc ("lipid-omics") |
AD7C (NTP) | Galasko | | CSF, plama | | | | | | 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 | | blood, CSF | | ELISA | | | | Consider all Ab, e.g., C-terminus-truncated; academic labs or potential future kit or PhRMA development (Takeda?) |
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CD59 | Rogers | | blood, CSF | | ELISA | | | | 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 | | serum, CSF | | immunoblot | | | 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 | | platelets from 27 mL blood | | immunoblot, densitometric | commercially available antibody (22C11) |
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Synaptic markers | Galasko | | CSF | | immunoblot | | | e.g., synaptophysin, synaptotagmin; no vendors |
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S100B | Mehta | | blood, CSF | | ELISA | | | | conflicting reports, results not reproducible |
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Neurofilaments, phospho | Galasko | | CSF | | ELISA | | | | antibodies are commercially available; assays by Hu, Iqbal, Rosengren |
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a - synuclein | Trojanowski | | CSF | | ELISA | | | | |
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Molecular chaperones | Trojanowski | | CSF | | | | | | e.g., Ubiquitin |
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8-OH-guanidine | Siemers | | CSF, plasma, urine | HPLC, GC/MS | | |
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