# Longitudinal Blood-based Transcriptomic Changes in AD: Relation to Clinical and Biomarker Data

> **NIH NIH U19** · MAYO CLINIC  JACKSONVILLE · 2023 · $780,461

## Abstract

ABSTRACT
Alzheimer’s disease (AD) is a progressive neurodegenerative condition leading to dementia. Despite intensive
efforts, there are no disease modifying therapies proven to arrest or slow the course. Numerous clinical trials
have failed due to incomplete understanding of pathophysiology, patient heterogeneity, and lack of precision in
selection strategies based on stage and other features for which widely accessible predictive biomarkers would
have a major impact. The overall goal of the U19 is to identify and validate Centrally-linked Longitudinal
pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations by integrating longitudinal multi-omics
and multimodal imaging and fluid endophenotypes from multiple independent cohorts. Project 2 will conduct the
first longitudinal blood-based multi-omics study of the well-characterized ADNI cohort including 4,120
biospecimens and up to 7 time points. ADNI is the only cohort study to our knowledge with whole genome
sequencing, longitudinal DNA and RNA samples, DNA methylation, metabolomics/lipidomics profiling and
proteomics, along with longitudinal multimodal neuroimaging, and fluid AD biomarkers on the same participants.
Based on our preliminary results, we hypothesize that we will be able to identify the relationship between
longitudinal molecular signature changes and longitudinal “A/T/N/V” (amyloid, tau, neurodegeneration, and
cerebrovascular) biomarker changes including network alterations in brain connectivity. The overarching goal of
Project 2 is to identify novel, non-invasive, centrally-linked molecular signatures that can serve as candidate
biomarkers suitable for early detection and design of tailored therapeutics supporting the future precision
medicine of AD/ADRD. A 3-Tier approach will 1) test 4 hypothesized biological pathways (immune, vascular,
myelination, synaptic integrity), 2) assess 20 additional ADRD pathways, and 3) discover novel molecular
signatures using an unbiased search and Artificial Intelligence (AI) strategies. Aim 1 is to identify molecular
signatures in peripheral blood associated with changes in cognitive status, both cross-sectionally and
longitudinally. Aim 2 will identify molecular signatures in blood associated with changes in A/T/N/V AD
biomarkers, both cross-sectionally and longitudinally. Aim 3 will assess the ability of multi-omics based molecular
profiling at baseline and over time to predict future disease progression. Aim 4 will replicate and validate ADNI
findings using blood- and brain tissue-based data (with Project 1) and data from multiethnic populations including
African- and Latino- American ancestry (with Project 3). Project 2 will employ an integrative translational
approach supported by the U19 Cores, combining longitudinal clinical, multi-omics, and AD biomarker data,
including advanced neuroimaging, to enable deeper mechanistic insights into the molecular basis of AD and to
identify new potential therapeutic targets and biomarker strat...

## Key facts

- **NIH application ID:** 10555728
- **Project number:** 1U19AG074879-01A1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** ANDREW J SAYKIN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $780,461
- **Award type:** 1
- **Project period:** 2023-03-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10555728

## Citation

> US National Institutes of Health, RePORTER application 10555728, Longitudinal Blood-based Transcriptomic Changes in AD: Relation to Clinical and Biomarker Data (1U19AG074879-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10555728. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*