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 GNA´s 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
Alzheimer´s 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 Alzheimer´s 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 Alzheimer´s 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-Gomez´s 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. Welti´s Lab
(scientific service) and Dr. Area-Gomez.
