Trends in Biomarker Diagnostics for Alzheimer’s Disease

Researchers believe that biomarkers offer one of the most promising paths for their ability to indicate early stages of Alzheimer’s. Read more about new developments and what's on the horizon in this Frost & Sullivan analysis.

Alzheimer’s disease is the leading cause of dementia. It adversely affects thought, memory and language functions and usually starts with mild cognitive impairment. In 2016, more than 45 million people around the world were afflicted with Alzheimer’s and related dementia; currently, no treatments can reverse the neurodegeneration. Several biological processes, such as oxidative stress and mitochondrial DNA mutations, are common to both aging and neurodegeneration. The prevalence of neurodegenerative disorders is likely to increase as the geriatric population grows globally. In the United States alone, according to The Alzheimer’s Association, healthcare costs for Alzheimer’s and related dementia was estimated to be about $259 billion in 2017 and is projected to rise to $1.1 trillion by 2050. 

Alzheimer’s diagnosis mostly relies on documenting mental decline. The disease poses a significant diagnostic challenge: current techniques can detect it only at the dementia stage. Diagnosis is usually the result of a combination of clinical examination, neuropsychological tests and brain imaging. Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans are the gold standard for affirmative diagnosis; optical scans that utilize retinal amyloid assessment are emerging as novel, cost-effective diagnostics. However, there is a large, unmet need for early diagnosis. Researchers believe that biomarkers offer one of the most promising paths; in fact, several potential biomarkers are being studied for their ability to indicate early stages of Alzheimer’s. Developments in blood and cerebrospinal fluid-based enzyme-linked immunosorbent assay (ELISA) and new genomic screening technologies are leading the emerging biomarker diagnostic platforms. 

Blood-Based ELISA for Early Diagnosis

Considerable progress has been made in demonstrating how biomarkers relate to the pathophysiology of Alzheimer’s; some include expensive and/or invasive putative disease markers obtained by MRI and PET, and those that require collection of cerebrospinal fluid (CSF) via lumbar puncture—a risky and invasive procedure. Still, a formal and definitive Alzheimer’s diagnosis can only be given by autopsy. There is a need for less expensive and intrusive, and widely available, blood-based (serum or plasma) biomarkers that can aid in early diagnosis and predict disease progression. 

Pre Diagnostics AS, a Norwegian diagnostics company that focuses on in-vitro diagnostics biomarker products for diagnosis of early Alzheimer’s, has developed a blood-based ELISA technique for analyzing mid-domain amyloid beta peptides (a widely studied plasma biomarker for Alzheimer’s) in macrophages. Clinical proof-of-concept studies using age-matched controls revealed that the test detects Alzheimer’s in the predementia stage. The novel test is minimally invasive and cost-effective compared with PET scans and CSF-based assays and is expected to present major opportunities in markets around the world. Tormod Fladby, the head of the neurology department at Akershus University Hospital and a professor of clinical medicine at the University of Oslo, is credited with the discovery. The company is working toward the commercialization of a blood macrophage-based immunoassay to detect Alzheimer’s.

Fluorescent Assay Kit for Detection

Amoneta Diagnostics, a French company, is working on a project called ADKIT to develop a peripheral blood-based diagnostic kit for Alzheimer’s using two blood biomarkers that are scientifically proven to be associated with disease. 

The test requires just a drop of blood for detection of biomarkers using the company’s proprietary fluorescent probes. Early clinical results revealed that the test has reliable sensitivity and specificity standards. The company aims to validate the so-called ADDIA diagnostic test via a proof-of-performance clinical study in human subjects. 

Amoneta Diagnostics is developing the test under an exclusive licensing agreement with the French National Centre for Scientific Research, which is the owner of the patent for this technology.  The project is funded by European Commission Horizon-2020, and is supported by patient organization Alzheimer Europe and several European Alzheimer’s centers that are enrolling study subjects.

Identifying Genetic Risk Variants for Mild Cognitive Impairment and Alzheimer’s

Cell cycle regulation defects can play an important role in the development of cancer, myocardial infarction, stroke, atherosclerosis, and neurodegenerative disorders. It is widely accepted that the pathogenesis of Alzheimer’s involves similar cell cycle mechanisms. In neurones, the progression  of  the  cell  cycle  is  normally  arrested  at  an  early  stage  and  they  are  not  able  to  redifferentiate. Failure of the arrest mechanisms are thought to be associated with the risk of Alzheimer’s. Related gene expression analysis could provide new insights.  

Cytox is a U.K.-based company that is developing diagnostic and prognostic platforms for Alzheimer’s and other dementias using single nucleotide polymorphism (SNP) profiling techniques. This technology involves the application of exome sequencing for identifying SNP that will be used with an algorithm to predict Alzheimer’s progression. Cytox and Affymetrix, a Thermo Fisher Scientific company based in Santa Clara, Calif., collaborated to co-develop and commercialize the blood-based assay platform that will aid the diagnosis and prognosis of mild cognitive impairment and Alzheimer’s.  The company plans a 2018 CE approval, and plans U.S. clinical launch by end of this year.

What’s the Future?

Global collaborations are critical to accelerate the development of biomarker-based diagnostic techniques. Advancements in omics-based technologies, such as genomics, proteomics and metabolomics, could lead to the development of novel blood-based biomarkers for better diagnosis. Researchers are working on validating reliable and inexpensive blood-based methods for early diagnosis, detection and monitoring of Alzheimer’s progression.

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