Final Report Summary - LOAD PROFILE (Development of a late-onset-Alzheimer’s disease (LOAD) profile for accurate diagnosis and identification of potential therapeutic approaches) Globally, nearly 44 million people suffer from dementia, most of which is attributable to age-related (late-onset) Alzheimer’s disease (LOAD). AD is characterised by severely impaired memory performance, pathological deposits in the brain, and changes in blood platelets. A number of factors play a role in the development of AD and, therefore, accurate diagnosis depends on a combination of several specific biomarkers. The main task of this project is to develop a blood test for routine diagnosis of LOAD. In detail, this project plans to develop blood platelet isolation devices, diagnostic tools (protein and DNA bio chips), and algorithms for establishing and interpreting a patient’s late-onset Alzheimer’s disease (LOAD) profile with specific blood biomarkers for routine analysis. Today, the best established biomarkers for AD are the decrease in Abeta peptides and increased levels of tau- and phospho-tau proteins in the cerebrospinal fluid. However, lumbar puncturing is an invasive and unpleasant procedure. Biomarkers based on easily obtainable blood samples would facilitate the work flow of AD diagnosis and prognosis of AD in aMCI patients. Platelets are an attractive source for AD blood biomarkers since they show several biochemical abnormalities associated with AD brain including similar pathological changed processing of the amyloid precursor protein. Additionally a number of genetics factors (ApoE4, BIN1, PICALM, CLU, GSTO1, which also can be analysed from blood, correlate with the risk to develop LOAD. Decreased vitamin B12, folate and increased homocysteine levels, detectable in cerebrospinal fluid as well as in blood plasma, are metabolic dysfunctions that may be linked to epigenetic changes in methylation patterns of LOAD relevant genes. This Industry academia partnership (IAPP) consisted of five partners, three are from academia and two are from industry to realise the development of a LOAD blood profile test. The University of Vienna identified metabolic LOAD markers in blood. The Medical University of Viennna performed complementary proteomic and (epi)genetic studies and generated algorithms for multi-arrays. Significant genetic aberrations in LOAD were translated into assays of a DNA chip at the diagnostic company Randox. In addition, the SME LEDO and the Politechnika Lodzka joined their expertise to develop a platelet isolation column kit for routine analysis. This Marie Curie IAPP project enabled intensive transfer of knowledge and was extremely helpful to develop prototype kits with great potential to detect highly accurate blood profiles for the diagnosis of LOAD. In the first period the platelet protein biochip was developed and successfully validated with 51 Alzheimer's disease and 51 cognitive healthy sex-and age matched control blood samples by the cooperation of the MUW and Randox. This translational biomarker work was published in August 2014 in the top Journal Acta Neuropathologica. To enable the routine diagnosis by this LOAD platelet protein chip LEDO and PL developed in this project phase a prototype platelet Isolation kit, which was also physically demonstrated on the midterm meeting. In the second period the platelet isolation device was tested with clinical blood samples and extracted platelet proteins could be analysed by the newly developed LOAD platelet protein chip. it was possible to submit a patent claim for legal security of this platelet isolation device described in document: EU 15461575.1-1651 “A Kit for Centrifugal Separation of Biological Fluid Components and a Method for Centrifugal Separation of Biological Fluid Components”, Walkowiak B., Szyma#ski W., Siatkowska M., Komorowski P., Olbrzymek L., Olbrzymek D., Olbrzymek J. LOAD-related blood profiles, detectable at the proteome as well as at the genetic level, were further successfully confirmed in new cohorts of 71 LOAD patients and 118 cognitive healthy matched controls. Additionally the prognostic value could be shown in 52 patients with mild cognitive impairment, which represent the pre-stage of LOAD. These valuable results in LOAD biomarker research were published in June 2016 in the section Gerotarget of the top free-access journal Oncotarget (https://www.ncbi.nlm.nih.gov/pubmed/27259244). Finally, an algorithm was developed which combined the LOAD biomarker profiles from the platelet protein and DNA biochip developed by Randox which raised the diagnostic accuracy compared to the algorithm of the single proteomic or genetic LOAD profiles.The Internet Adresse of the Project Homepage is: http://www.alzheimer-profile.eu/The name of the project coordinator and contact person is: Maria ZellnerLOAD Logo is attached
