Biomarkers and methods relating to Alzheimer's disease

Inventors

Ward, Malcolm Andrew • Hye, Abdul • Lovestone, Simon Harold • Dobson, Richard James Butler

Assignees

Kings College London • Proteome Sciences PLC

Abstract

Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.

Core Innovation

The invention concerns biomarker panels and related diagnostic kits for Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD). The kits comprise reagents for the detection of a set of biomarkers in a tissue or body fluid sample, and the disclosed biomarker set includes transthyretin (TTR), Clusterin, Cystatin C (CST3), Alpha-1-Acid glycoprotein (A1AG1), Intercellular adhesion molecule 1 (ICAM1), Complement C4 (CC4), pigment epithelium derived factor (PEDF), Alphal antitrypsin (A1AT), regulated on activation, normal T cell expressed and secreted (RANTES), and Apolipoprotein C-III (ApoC3).

The reagents include a plurality of primary antibodies, where each primary antibody specifically binds to a different biomarker in the set of biomarkers. The kit is configured to allow detection using an ELISA assay or Western blotting to determine a presence or a level of expression of each biomarker.

In at least one kit configuration, the detection reagents are additional antibody components and optional assay support. Further kit embodiments include control samples for each biomarker, with each control sample containing a specified amount or concentration of the biomarker taken from healthy individuals and from patients having MCI and/or AD, including conditions for patients not treated with an MCI/AD therapeutic agent.

Claims Coverage

Two independent claims are provided. The coverage centers on an antibody-based diagnostic kit defined by a specified biomarker set, with one independent claim explicitly reciting ELISA and Western blot detection using primary antibodies.

Across the independent claims, the coverage centers on a diagnostic kit that uses a plurality of primary antibodies, each binding a distinct biomarker from a defined TTR/Clusterin/CST3/A1AG1/ICAM1/CC4/PEDF/A1AT/RANTES/ApoC3 panel, with detection configured via ELISA and/or Western blotting.

Stated Advantages

Documented Applications