Methods for diagnosis of Alzheimer's Disease in blood samples
First Claim
Patent Images
1. A method of aiding diagnosis of Alzheimer'"'"'s disease (“
- AD”
), comprising comparing normalized measured levels of at least forty-six AD diagnosis biomarkers in a blood sample from a human individual seeking a diagnosis for AD to reference levels for the at least forty-six biomarkers in the blood sample,wherein the human individual has a Mini Mental State Exam (MMSE) score of 14-26,wherein the reference levels are obtained from normalized measured values of the at least forty-six biomarkers from samples in the blood of human individuals without AD,wherein the at least forty-six AD diagnosis biomarkers comprise;
GCSF (granulocyte-colony stimulating factor);
IFN-g (interferon-gamma);
IGFBP-1 (insulin-like growth factor binding protein
1);
BMP-6 (bone morphogenetic protein
6);
BMP-4 (bone morphogenetic protein
4);
Eotaxin-2;
IGFBP-2 (insulin-like growth factor binding protein
2);
TARC (thymus and activation-regulated chemokine);
RANTES;
ANG (angiogenin);
PARC (pulmonary and activation-regulated chemokine);
Acrp30 (adipocyte complement-related protein of 30 kDa);
AgRP(ART) (agouti-related protein (agouti-related transcript));
TIMP-1 (tissue inhibitor of metalloproteinase
1);
TIMP-2 (tissue inhibitor of metalloproteinase
2);
ICAM-1 (intercellular adhesion molecule
1);
TRAIL R3 (tumor necrosis factor-related apoptosis-inducing ligand receptor
3);
uPAR (urokinase-type plasminogen activator receptor);
IGFBP-4 (insulin-like growth factor binding protein
4);
LEPTIN(OB);
PDGF-BB (platelet-derived growth factor BB);
EGF (epidermal growth factor);
BDNF (brain-derived neurotrophic factor);
NT-3 (neurotrophin
3);
NAP-2(neutrophil-activating peptide
2);
IL-1ra (interleukin 1 receptor antagonist);
MSP-a (macrophage stimulating protein alpha);
SCF (stem cell factor);
TGF-b3 (transforming growth factor, beta
3);
TNF-b (tumor necrosis factor beta);
MIP-1d;
IL-3 (interleukin
3);
FGF-6 (fibroblast growth factor
6);
IL-6 R (interleukin-6 receptor);
sTNF RII (soluble tumor necrosis factor receptor II);
AXL;
bFGF (basic fibroblast growth factor);
FGF-4 (fibroblast growth factor
4);
CNTF (ciliary neurotrophic factor);
MCP-1(monocyte chemoattractant protein
1);
MIP-1b (macrophage inflammatory protein-1beta);
TPO (thrombopoietin);
VEGF-B (vascular endothelial growth factor B);
IL-8 (interleukin
8);
FAS; and
EGF-R (epidermal growth factor receptor),whereby the diagnosis of AD is aided by determining a difference between the normalized measured levels of the at least forty-six AD diagnosis biomarkers to the reference levels of the at least forty-six biomarkers from non-AD samples wherein the difference meets or exceeds a statistically significant difference between normalized measured values of the at least forty-six AD diagnosis biomarkers in the blood samples from individuals without AD and individuals with AD, wherein the statistically significant difference indicates a diagnosis of AD.
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Abstract
The inventors have discovered a collection of proteinaceous biomarkers (“AD biomarkers) which can be measured in peripheral biological fluid samples to aid in the diagnosis of neurodegenerative disorders, particularly Alzheimer'"'"'s disease and mild cognitive impairment (MCI). The invention further provides methods of identifying candidate agents for the treatment of Alzheimer'"'"'s disease by testing prospective agents for activity in modulating AD biomarker levels.
41 Citations
17 Claims
-
1. A method of aiding diagnosis of Alzheimer'"'"'s disease (“
- AD”
), comprising comparing normalized measured levels of at least forty-six AD diagnosis biomarkers in a blood sample from a human individual seeking a diagnosis for AD to reference levels for the at least forty-six biomarkers in the blood sample,wherein the human individual has a Mini Mental State Exam (MMSE) score of 14-26, wherein the reference levels are obtained from normalized measured values of the at least forty-six biomarkers from samples in the blood of human individuals without AD, wherein the at least forty-six AD diagnosis biomarkers comprise;
GCSF (granulocyte-colony stimulating factor);
IFN-g (interferon-gamma);
IGFBP-1 (insulin-like growth factor binding protein
1);
BMP-6 (bone morphogenetic protein
6);
BMP-4 (bone morphogenetic protein
4);
Eotaxin-2;
IGFBP-2 (insulin-like growth factor binding protein
2);
TARC (thymus and activation-regulated chemokine);
RANTES;
ANG (angiogenin);
PARC (pulmonary and activation-regulated chemokine);
Acrp30 (adipocyte complement-related protein of 30 kDa);
AgRP(ART) (agouti-related protein (agouti-related transcript));
TIMP-1 (tissue inhibitor of metalloproteinase
1);
TIMP-2 (tissue inhibitor of metalloproteinase
2);
ICAM-1 (intercellular adhesion molecule
1);
TRAIL R3 (tumor necrosis factor-related apoptosis-inducing ligand receptor
3);
uPAR (urokinase-type plasminogen activator receptor);
IGFBP-4 (insulin-like growth factor binding protein
4);
LEPTIN(OB);
PDGF-BB (platelet-derived growth factor BB);
EGF (epidermal growth factor);
BDNF (brain-derived neurotrophic factor);
NT-3 (neurotrophin
3);
NAP-2(neutrophil-activating peptide
2);
IL-1ra (interleukin 1 receptor antagonist);
MSP-a (macrophage stimulating protein alpha);
SCF (stem cell factor);
TGF-b3 (transforming growth factor, beta
3);
TNF-b (tumor necrosis factor beta);
MIP-1d;
IL-3 (interleukin
3);
FGF-6 (fibroblast growth factor
6);
IL-6 R (interleukin-6 receptor);
sTNF RII (soluble tumor necrosis factor receptor II);
AXL;
bFGF (basic fibroblast growth factor);
FGF-4 (fibroblast growth factor
4);
CNTF (ciliary neurotrophic factor);
MCP-1(monocyte chemoattractant protein
1);
MIP-1b (macrophage inflammatory protein-1beta);
TPO (thrombopoietin);
VEGF-B (vascular endothelial growth factor B);
IL-8 (interleukin
8);
FAS; and
EGF-R (epidermal growth factor receptor),whereby the diagnosis of AD is aided by determining a difference between the normalized measured levels of the at least forty-six AD diagnosis biomarkers to the reference levels of the at least forty-six biomarkers from non-AD samples wherein the difference meets or exceeds a statistically significant difference between normalized measured values of the at least forty-six AD diagnosis biomarkers in the blood samples from individuals without AD and individuals with AD, wherein the statistically significant difference indicates a diagnosis of AD. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
- AD”
Specification