IMPLEMENTATION OF BIOFLUID MARKERS FOR EARLY DETECTION OF ALZHEIMER'S DISEASE AND OTHER NEURODEGENERATIVE DISEASES IN COLOMBIA

The primary aim of this supplement request is to complete and to strengthen the use of biofluid markers for Alzheimer's disease and other neurodegenerative diseases in Colombia, integrating them into routine clinical practice and research studies. Our focus is on enhancing the capabilities of the Neuroscience Group of the University of Antioquia (GNA)

to support the biofluid markers core in Colombia and the broader Latin American region, because Antioquia and rest of Colombia are in a privileged situation by unique and/or bigger population carrying on diverse and causative gene of neurodegenerative diseases. Under our current 1R21AG079574-01 initiative, we could diligently imported SIMOA

equipment not before than January 21st, 2024 and warranty issues delayed the final installation until the next may 13th-14th, and we will have the training on may 21-24 2024 for standardizing and validating the reproducibility of biofluid markers in the study population. Therefore, we will need a year more with administrative supplements to successfully

complete the research project activities and to obtain the full productivity at the end of the supplement and submit the continuity of the research through a RO1 research project grant application. Because there is a need to realize the analyze of serum by SIMOA, to complete and to increase the ns by lipidome using MS; further stratify clinical histories, compare, and

validate the sensitivity and robustness of biomarker detection, and establish cut-offs in our local site. This is crucial for collaboration and the development of new clinical research aimed at the prognostic and primary prevention of Alzheimer's disease and other neurodegenerations. Our current focus involves utilizing blood tests to streamline the identification of Alzheimer's

and other neurodegenerative diseases' fluid biomarkers in a faster and more cost-effective manner in Colombia and in the LATAM region. Under our ongoing initiative, 1R21AG079574-01, we are conducting installation, standardization, comparison of preliminary analyses with high-sensitivity detection of biofluid markers using SIMOA-

Quanterix with lipidome profile. However, we need to continue for complete our analysis categorized by genotype (PS1 variants and APOE isoforms), sex, and age range (8-12, 13- 19, 20-30, 30-40, and older 41yo symptomatic and asymptomatic). This approach will validate the sensitivity, specificity, and reproducibility of our measurements, establishing a

transversal paired correlation with a lipidome profile as the basis for understanding the etiopathogenesis and looking for the specific targeting for primary prevention. We need to achieve robustness of our results; because the preliminary ones suggest the novelty finding that lipidome signature is earlier and sensible to discriminate between

carriers and non-carriers’ population both in men and women at eight years old, respect to protein biofluid markers showed over 20 yo. Importantly, higher baseline P-tau217 levels predicted subsequent elevations in in vivo amyloid and tau pathology, as well as memory decline over time in carriers. These findings

strengthen the case for plasma P-tau217 as a potential non-invasive diagnostic and prognostic biomarker for AD, with implications for clinical practice and trials. That complementary to the future prodromal lipid signature will guide earlier and more sensible biofluid marker detection for pronostic, diagnostic, health care, primary prevention and

treatments. The Colombian team, led by Drs. Lopera (Coinvestigator) and Cardona (PI), will establish SIMOA technology, creating the necessary infrastructure for a reference center capable of detecting and quantifying blood biomarkers, considering the privilege and enrichment genetic cases of neurodegenerative diseases in the LATAM region. This collaborative effort

with Dr. Estela Area-Gomez (coinvestigator) from Columbia University (also from the CIB- CSIC,Spain) and Dr Yakeel Quiroz as significant collaborator in the MGH, we will explore new biomarkers suggested by lipidome analysis, building expertise in advanced methods at the region for future health care, prevention and treatment programs.