Fluid Biomarker Core

PROJECT SUMMARY – BIOMARKER (FLUID) CORE (BMC) During the NMeADRC, we identified specific MRI- and fluid- based biomarkers to classify ADRDs into vascular and neurodegenerative contributions. Currently, AD diagnosis uses the NIA/AA formula with A+ (A), T+ (phosphorylated tau at threonine 181), and N+ (neurodegeneration) as surrogates in diagnosis. These require

invasive lumbar puncture for cerebrospinal fluid or costly Positron Emission Tomography scans. The BMC has two ultrasensitive assay instruments, MesoScale Discovery and Quanterix HD-X, to assay for plasma biomarkers, such as neurofilament light (NfL) and glial acidic fibrillary protein (GFAP). In addition, we have

measured blood-brain barrier (BBB) permeability with dynamic contrast-enhanced MRI (DCEMRI) and albumin index as an indicator of inflammation. Importantly, biomarkers improve patient classification. We developed a clustering method to separate patients based on CSF AD proteins and MRI white matter injury (the double

dichotomy method) that classified subjects into AD, VCID, MX, and controls. We have further improved this approach with a larger cohort from the ADNI database and the addition of a cognitive axis (trichotomy method). This expands the diagnostic formula to ATNVI formula by adding neurovascular (V) and neuroinflammatory

biomarkers (I). The availability of plasma-based biomarkers will be a major benefit for the rural populations in New Mexico. They will allow for population screening for early AD patient inclusion in the emerging clinical trials for AD. This focus on vascular disease and inflammation is especially important in the minority populations of

rural New Mexico because of the high incidence of vascular disease in this population. Early identification of at- risk individuals we provide the basis for studies of prevention in these populations of Hispanics/Latinos (H/L) and American Indians (AI) that are rarely included in such studies. The BMC will also share fluid samples and

biomarker data (where allowed) with NACC to support national initiatives in understanding the etiological factors of AD/ADRDs in diverse populations and thus meet the goals of NAPA. The specific aims of the BMC are Aim 1: To establish a state-of-the-art infrastructure for sample collection, biobanking, biomarker analysis, and

prioritization to assess AD/ADRD risk and early onset and to track progression. Aim 2: To validate the plasma- based biomarkers by correlation with indicators of inflammation developed in MarkVCID and cognitive impairment from neuropsychological testing. Patients with multiple etiology dementia will be identified by injury

to the white matter shown by MRI and AD proteins in the blood. We will develop a pipeline for sharing resources and supporting developmental work on AD/ADRD at UNM and across New Mexico. Aim 3: To integrate with other Cores to identify risk factors, prevalence, and prognosis of AD/ADRDs using plasma-based biomarkers to

improve diagnosis and care of the medically underrepresented rural populations of New Mexico and to use the resources at the NM ADRC to train the next generation of researchers.