Methods and kits for the differential diagnosis of Alzheimer's disease versus frontotemporal dementia and for the diagnosis of frontotemporal dementia, comprising FAS-L and CK 18 as biomarkers

• US 8,753,607 B2
• Filed: 07/19/2011
• Issued: 06/17/2014
• Est. Priority Date: 03/21/2008
• Status: Active Grant

• Current Assignee: Manuela G. Neuman
• Original Assignee: Manuela G. Neuman
• Inventors: Neuman, Manuela G.
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): MACFARLANE, STACEY NEE
• Application Number:
  US13/185,831
• Publication Number:
  US 20120015381A1
• Time in Patent Office: 1,064 Days
• Field of Search: None
• US Class Current: 424/9.1
• CPC Class Codes: G01N 2333/4742 Keratin; Cytokeratin
• CPC Class Codes: G01N 2333/525 Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 2333/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153 or CD154
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention relates to methods and kits for the differential diagnosis of Alzheimer'"'"'s disease (AD) versus frontotemporal dementia (FTD), using biomarkers TNF-α, FAS-L and CK18, taken from a biological sample. Differences in biomarker levels can be used to distinguish between AD and FTD The invention is based on a discovered correlation between FTD and markers FAS-L and CK18. Therefore the invention also relates to the diagnosis of FTD using FAS-L and CK18. The serum concentrations of these biomarkers can further be used as an index of the severity of disease, and may occur in conjunction with clinical-based diagnostic testing and neuro-imaging assessment.

Claims

1. A diagnostic kit for determining a differential diagnosis in a non-invasive manner in an individual of Alzheimer'"'"'s disease (AD) versus frontotemporal dementia (FTD) consisting of:

a) reagents specific for TNF-α

, FAS-L, and caspase-cleaved CK18,

b) instructions for use of the reagents to determine levels of said TNF-α

, FAS-L, and caspase-cleaved CK18 in biological samples obtained from such individual,

c) optionally, a reference substance for each of said TNF-α

, FAS-L, and caspase-cleaved CK18 for normalizing data, and

d) an information sheet for comparing measured levels of said TNF-α

, FAS-L, and caspase-cleaved CK18 to reference levels for each of said TNF-α

, FAS-L, and caspase-cleaved CK18 to determine whether said individual is suffering from AD or FTD, and/or

e) an information sheet for comparing the levels of TNF-α

, FAS-L and caspase-cleaved CK18 to reference levels for each of said TNF-α

, FAS-L and caspase-cleaved CK18 relating to severity of AD or FTD to determine the severity of AD or FTD in said individual.

2. The diagnostic kit of claim 1, wherein said biological samples are peripheral blood samples.

3. The diagnostic kit of claim 1, wherein said information sheets indicate that

i) a measured level of TNF-α

of from about 80 pg/mL to 90 pg/mL is indicative of possible AD;

ii) a measured level of TNF-α

of from about 90 pg/mL to about 120 pg/mL is indicative of mild AD;

iii) a measured level of TNF-α

of from about 120 pg/mL to 140 pg/mL is indicative of moderate AD;

iv) a measured level of TNF-α

greater than 140 pg/mL is indicative of severe AD;

v) a measured level of FAS-L of from about 70 pg/mL to about 80 pg/mL is indicative of mild FTD;

vi) a measured level of FAS-L of from about 81 pg/mL to about 105 pg/mL is indicative of moderate FTD;

vii) a measured level of FAS-L of greater than 105 pg/mL is indicative of severe FTD; and

viii) a measured level of caspase-cleaved CK18 above 100 U/1000 mL is indicative of FTD.

4. A diagnostic kit for detecting frontotemporal dementia (FTD) in an individual consisting of:

a) reagents specific for FAS-L and caspase-cleaved CK18,

b) instructions for use of the reagents to determine levels of said FAS-L and caspase-cleaved CK18 in biological samples obtained from an individual,

c) optionally, a reference substance for each of said FAS-L and caspase-cleaved CK18 for normalizing data, and

d) an information sheet for comparing the levels of FAS-L and caspase-cleaved CK18 to reference levels for each of said FAS-L and caspase-cleaved CK18 relating to severity of FTD to determine the severity of FTD in said individual.

5. The diagnostic kit of claim 4, wherein said biological samples are peripheral blood samples.

6. The kit of claim 4, wherein said information sheets indicate that

i) a measured level of FAS-L of from about 70 pg/mL to about 105 pg/mL is indicative of mild to moderate FTD;

ii) a measured level of FAS-L greater than 105 pg/mL is indicative of severe FTD; and

iii) a measured level of caspase-cleaved CK18 above 100 U/1000 mL is indicative of FTD.