Project Grant R21AG079574

IMPLEMENTATION OF BIOFLUID MARKERS FOR EARLY DETECTION OF ALZHEIMER'S DISEASE AND OTHER NEURODEGENERATIVE DISEASES IN COLOMBIA - BIOMARKER FLUIDS ARE A LESS EXPENSIVE OPTION FOR STUDYING THE AD AND OTHER NEURODEGENERATIVE DISEASES POPULATIONS. HOWEVER, WE HAVE NOT AVAILABLE THIS TECHNOLOGY FOR HELPING TO THE EARLY OR ANTEMORTEM DIAGNOSIS, AND ALSO FOR THE SUPPORT OF NEW FINDINGS AND PERIPHERAL BIOMARKERS PROPOSALS. THE MAIN AIM OF THIS PROJECT IS TO ENHANCE THE FUTURE CAPABILITY OF THE NEUROSCIENCE GROUP OF THE UNIVERSITY OF ANTIOQUIA (GNA) TO DEVELOP NEW CLINICAL RESEARCH FOR THE PREVENTION OF ALZHEIMER'S DISEASE. OUR INSTITUTION HAS BEEN INTERNATIONALLY RECOGNIZED FOR ITS CLINICAL RESEARCH TRAJECTORY. HOWEVER, IN ORDER TO TAKE FULL ADVANTAGE OF OUR WELL-CHARACTERIZED HUMAN BRAIN GNAS BIOBANK WITH THE LARGEST COLLECTION AVAILABLE WORLDWIDE OF BIOLOGICAL SAMPLES WITH FAMILIAL ALZHEIMER'S DISEASE (AD) AND OTHER NEURODEGENERATIVE CONDITIONS. OUR RESEARCH INFRASTRUCTURE REMAINS IN NEED TO IMPROVE ITS BASIC-BENCH RESEARCH CAPABILITIES. USING THESE UNIQUE SAMPLES COHORTS, OUR ULTIMATE GOAL IS TO ESTABLISH THE NECESSARY INFRASTRUCTURE TO IMPLEMENT THE USE OF BIOFLUID MARKERS FOR ALZHEIMERS DISEASE AND OTHER NEURODEGENERATIVE DISEASES IN COLOMBIA, FOR FUTURE CLINICAL RESEARCH STUDIES AND THE EARLY DETECTION, DIAGNOSIS, PREVENTION AND TREATMENT OF AD IN THE COUNTRY. SPECIFICALLY, I) WE WILL ESTABLISH THE INFRASTRUCTURE FOR THE DETECTION OF BIOMARKERS IN BLOOD (PLASMA AND SERUM) OF INDIVIDUALS WITH FAMILIAL ALZHEIMERS DISEASE (AD). THE COLOMBIAN TEAM, LED BY DRS. LOPERA (CO-PI) AND CARDONA (PI) WILL TRANSFER SIMOA TECHNOLOGY TO ASSEMBLE THE NECESSARY INFRASTRUCTURE TO STANDARDIZE THE DETECTION AND QUANTIFICATION OF BLOOD BIOMARKERS SUCH AS: AMYLOID BETA (AB) 40/AB42, TOTAL TAU, PTAU-181, NFL, GFAP, SNAP-25 FROM QUANTERIX. IN COLLABORATION WITH DR YAKEEL QUIROZ (CO-PI), STEVEN ARNOLD (CO-INVESTIGATOR), INVESTIGATORS FROM THE COLOMBIAN TEAM WILL GET TRAINING IN ADVANCED METHODS FOR THE DETECTION OF BLOOD BIOMARKERS AND THEIR ASSOCIATION WITH THE PROGRESSION OF NEURODEGENERATION AND COGNITIVE DECLINE IN ALZHEIMER'S DISEASE AND OTHER DEMENTIAS. ALSO, II A) WE WILL DETERMINE EARLY BIOMARKERS IN A COHORT OF FAMILIAL ALZHEIMERS PATIENTS CARRYING HIGHLY PENETRANT MUTATIONS AND AD-ASSOCIATED GENE VARIANTS. IN ORDER TO IDENTIFY EARLY BIOMARKERS OF AD, CAPABLE OF MONITORING DISEASE PROGRESSION FROM CARRIERS AND NON-CARRIERS OF PSEN1 MUTATIONS, ALSO INCLUDING DIFFERENT PATHOGENIC PSEN1 MUTATIONS, AS WELL AS PATHOGENIC AND PROTECTIVE VARIANTS AND MEMBERS WITH LATE-ONSET AD. FINALLY, BASED AT THE HYPOTHESIS THAT: "PHOSPHOLIPIDS (PL) COMPOSITION AT THE ENDOMEMBRANE SYSTEM OF THE NEURAL CELLS REPORT EARLY MODIFICATIONS OF THE NEUROVASCULAR UNIT ALTERATION TO THE PERIPHERY", II B) WE WILL EXPLORE THE STANDARDIZATION OF NEW PERIPHERAL MARKERS FOR EARLY PREDICTION OF DEMENTIA. WE WILL USE HIGH RESOLUTION MASS SPECTROMETRY (MS) TO VALIDATE OUR PRELIMINARY DATA ON THE PHOSPHOLIPID PROFILE AND FATTY ACID COMPOSITION OF SERUM FROM E280A-FAMILIAL AD PATIENTS IN FOUR DIFFERENT STAGES (8-12 YO, 13-19 YO, 20-30 YO, 30-40 YEARS OLD AND SYMPTOMATIC 40 Y OLDER, AND SPORADIC PATIENTS) AND AGED-MATCHED ASYMPTOMATIC CARRIERS AND NON-CARRIER CONTROLS. THESE SAMPLES WILL BE OBTAINED FROM THE BIOBANK OF "GROUP OF NEUROSCIENCE DE ANTIOQUIA" AND FROM STRONG COLLABORATION WITH DR. AREA-GOMEZS LAB AT COLUMBIA UNIVERSITY (CO-RESEARCHER). WE WILL OPTIMIZE A MULTIVARIATE STATISTICAL ANALYSIS AND ALGORITHM OF PREDICTION TO DEFINE THE ASSOCIATION BETWEEN AGE, GENOTYPE, COGNITIVE PERFORMANCE AND PHOSPHOLIPIDIC PROFILE. ALL LIPIDOMICS STUDIES WILL BE PERFORMED IN COLLABORATION WITH THE LIPIDOMIC CENTER OF KANSAS UNIVERSITY BETWEEN DR. WELTIS LAB (SCIENTIFIC SERVICE) AND DR. AREA-GOMEZ.