| Analyte |
Volunteer |
|
Matrix |
|
Method |
|
est Cost $ |
|
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 |
|
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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|
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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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|
|
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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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| |
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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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|
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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 |
|
|
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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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| |
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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 |
|
|
|
|
|
|
|
|
|
|
| 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 |
|
|
|
|
|
|
|
|
|
|
| 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 |
| |
|
|
|
|
|
|
|
|
|
| a - synuclein |
Trojanowski |
|
CSF |
|
ELISA |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Molecular chaperones |
Trojanowski |
|
CSF |
|
|
|
|
|
e.g., Ubiquitin |
|
|
|
|
|
|
|
|
|
|
| 8-OH-guanidine |
Siemers |
|
CSF, plasma, urine |
HPLC, GC/MS |
|
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