Alzheimer’s Disease: A Quest to Know More Fuels Biomarker Search

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Alzheimer’s Disease: A Quest to Know More Fuels Biomarker Search

KaloramaThe quest to diagnose and to affect the progress of Alzheimer’s relies on better research, according to Kalorama Information. For Alzheimer’s to be solved, knowledge about the disease must be improved, and that means biomarker search efforts should persist near-term, according to the healthcare market research firm. Nervous system or neurological biomarkers are covered in the Kalorama Information’s report Proteomics Research Markets.

“An incomplete understanding of the causes behind the diseases from a systems biology standpoint has also stalled clinical diagnostics development, even when CNS samples such as cerebrospinal fluid (CSF) are available,” said Kalorama Information analyst Emil Salazar in a recent blog post.

The debilitating neurodegenerative diseases Alzheimer’s and Parkinson’s have vexed healthcare in terms of both therapy and definitive antemortem diagnosis. The localized nature of the diseases in the central nervous system (CNS) makes the development of in vitro diagnostic (IVD) tests difficult. The incentive to develop marketable clinical assays has also been diminished to an extent by a lack of curative therapies for neurodegenerative diseases; clinicians are less apt to request or use a lab test to direct decision making for a disease without curative therapies.

Still, clinical value exists for diagnostics able to detect pre-symptomatic onset of Alzheimer’s and Parkinson’s and inform earlier implementation of palliative care and neuroprotective therapy. Kalorama Information said nervous system biomarkers are the second-fastest growing segment in the clinical and research biomarkers markets. Researchers have heavily targeted Alzheimer’s Disease (AD) diagnostics development using CSF samples and even skin samples.

Kalorama notes a few examples of efforts under way:

One study in Mexico took skin biopsies from patients with Alzheimer’s, Parkinson’s and non-Alzheimer’s dementia as well as similarly aged healthy patients and used immunohistochemistry (IHC) tests to assay levels of tau protein. The biomarker was found to be significantly elevated in the skin samples of Alzheimer’s and Parkinson’s patients; alpha-synuclein protein was also found to be elevated in the samples of Parkinson’s patients. Skin samples are theorized to be feasible proxies for brain tissue because of the samples’ common origin in embryonic development.

Another study identified protein kinase C epsilon (PKCe) as a biomarker for AD with reduced levels observed in AD patient skin samples. Development-stage therapeutics company Neurotrope is interested in a PKCe modulator as a potential treatment for AD patients. While CSF biomarker tests for AD are further along in development, skin biopsy tests would be much more widely implementable in healthcare.

Amarantus Bioscience offers a blood-based assay as a non-invasive alternative to CSF-based AD tests. The Lymphocyte Proliferation (LymPro) assay is able to differentiate AD individuals from other forms of dementia and healthy individuals by measuring the expression of CD69 protein during stimulated lymphocyte mitosis or cell division. In AD individuals, CD69 expression is down regulated compared to healthy individuals and those with other forms of dementia. The lymphocyte cell surface CD69 markers are measured using flow cytometry. In the test, peripheral blood lymphocytes are used as surrogates for neurons that theoretically exhibit the same cell cycle dysfunction.

Researchers at Merck have seized upon MS to meet evolving protein analysis demands, selecting immunoaffinity microflow LC-triple quad MS to identify different isoforms of tau biomarkers arising from post-translational modification. Immunoassays do not provide the specificity necessary to identify tau modifications that potentially influence disease progression.

Thermo Fisher has applied its own immunoenrichment triple quad MS approach for low-abundance blood proteins to the discovery and  monitoring of AD biomarkers. Researchers have used Thermo’s multiplexed mass spectrometric immunoassay (MSIA)-SRM assays for the quantitation of aberrant ceruloplasmin (affects homeostasis of free copper and results in AD-associated protein degradation and aggregation) and apolipoprotein E (promotes AD-associated beta amyloid fibril formation).