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Development of a late-onset-Alzheimer’s disease (LOAD) profile for accurate diagnosis and identification of potential therapeutic approaches

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New biochip test relieves the LOAD of Alzheimer's

No tests exist for early diagnosis of the late form of Alzheimer's disease that strikes after the age of 70. Ageing of the European population means that the incidence of this late-onset disease variant is likely to increase four-fold in the next 50 years.

Fundamental Research
Health

The neurodegenerative disorder late-onset Alzheimer’s disease (LOAD) currently affects 2 % of the population in industrialised countries. Early diagnosis and appropriate therapy to improve the condition of LOAD patients is urgently needed. Previous studies have found that LOAD is age-related and a result of many factors. Two of these are protein-related – a reduction in beta amyloid and an increase in hyperphosphorylated tau protein. Unfortunately, testing involves the use of cerebrospinal fluid from a lumbar puncture, a difficult procedure for this age group. The LOAD PROFILE project has developed a blood-based test. They looked at two cohorts with a total of more than 120 LOAD patients and 170 cognitively healthy volunteers that matched for sex and age. Using information from the scientists' previous research, the test detects proteins in blood platelets that reflect the metabolism of nerve cells or neurons. Additionally, the researchers added a number of genetic factors traceable in blood, decreased vitamin B12 and folate levels as well as epigenetic effects as a result of metabolic dysfunctions. After identification of the range of markers, researchers generated algorithms for multi-arrays and significant genetic variants in LOAD were translated into assays for a DNA chip. In addition, the LOAD PROFILE project developed a prototype platelet isolation column kit for routine analysis. The platelet isolation device was tested with clinical blood samples and extracted platelet proteins analysed by the newly developed LOAD platelet protein chip. On this basis, the project has submitted a patent claim for legal security of this platelet isolation device. Additionally, the prognostic value was demonstrated in 52 patients with mild cognitive impairment, which represents the pre-stage of LOAD. Increased diagnostic accuracy was achieved by an algorithm, which combines the LOAD biomarker profiles from the platelet protein and DNA biochip. Results have been published in the high-profile journals Journal Acta Neuropathologica and Oncotarget. The research promises to lead to prompt diagnosis with a simple blood test and new therapies for this neurodegenerative disease.

Keywords

Biochip, late-onset Alzheimer’s disease, LOAD PROFILE, blood-based test, patent, single nucleotide polymorphism, protein abundance, algorithm

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