# Measuring neurodevelopmental effects of polygenic risk for Alzheimer's disease via longitudinal study of brain and cognitive variables in periadolescent children

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $579,890

## Abstract

Project Summary/Abstract
Alzheimer’s disease (AD) is a devastating, progressive neurological disorder that selectively degrades the
cognition of many older adults — 6.1 million are living with AD in the US today and the estimated prevalence
by 2050 is 12.7 million. Patients diagnosed with AD often live 8-10 years with the disease, but declines in
memory and other cognitive abilities mean that patients face loss of independence and high costs of care
(estimated to be $186 billion in 2018). Management of AD risk with targeted interventions is a needed part of
our public health response, and genetic factors affecting AD risk will be essential to those efforts because they
are present throughout the lifespan. Critically, it is possible that genetic AD risk factors may bias brain and
cognitive development to increase vulnerability to AD later in life. A putative neurodevelopmental influence of
genes on AD vulnerability would be consistent with 1) the predictive power of early cognitive ability for later AD
risk, and 2) wide variability in how AD pathology (e.g., Aβ deposition) relates to AD symptomology (e.g.,
memory loss). Here, we hypothesize that genomic AD risk alters neurodevelopment of the brain systems
most affected by AD in ways that increase AD vulnerability. If true, then properties of AD-affected brain
structures and brain networks such as the hippocampus and functionally-coupled memory networks will vary
with genetic AD risk even during youth. Measuring how genetic factors affect brain development will elucidate
lifelong trends for AD risk while highlighting new opportunities for early intervention.
The project lead is a new, early-stage investigator with a background in the cognitive neuroscience of memory
and expertise in methods including neuroimaging and neuropsychology. In this study the investigators will
apply these methods to the study of early polygenic effects on neurodevelopment that may affect the risk of
late-onset neurodegenerative diseases including AD. Key preliminary data from large developmental datasets
have provided important early support for this hypothesis, and the current proposal describes a new, tightly
focused project designed to fill critical gaps in our existing knowledge. The Specific Aims are: 1) Measure
effects of AD-related genes on developmental differences in AD-vulnerable brain regions; 2) Quantify how
genes affect development of functional brain networks that are later vulnerable to AD; 3) Test developmental
differences in AD-vulnerable cognitive abilities attributable to AD-related genes. For these Aims, the research
team will develop a new dataset from a large sample (N=270) of healthy youths aged 9, 11, or 13 years by
combining neuroimaging (brain structure/function), neuropsychological tests (cognition), and genomic assays
(AD-related genes) in a longitudinal design. These data will improve the field’s understanding of the pressing
clinical problem of AD from a developmental risk perspective. While ...

## Key facts

- **NIH application ID:** 9973055
- **Project number:** 5R01AG064247-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** David E Warren
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $579,890
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973055

## Citation

> US National Institutes of Health, RePORTER application 9973055, Measuring neurodevelopmental effects of polygenic risk for Alzheimer's disease via longitudinal study of brain and cognitive variables in periadolescent children (5R01AG064247-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973055. Licensed CC0.

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