# Quantifying neurodevelopmental effects of polygenic risk for Alzheimer's disease via cross-sectional study of brain and cognition in periadolescent children

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $243,128

## Abstract

PROJECT SUMMARY/ABSTRACT: Research Project (D)
Alzheimer’s disease (AD) is a devastating, progressive neurological disorder that selectively degrades the
cognition of many older adults — 5.4 million are living with AD in the US today and the estimated prevalence
by 2050 is 13.8 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 for
healthcare ($160 billion in 2016). Management of AD risk with targeted interventions is a needed part of our
public health response, and attention to 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 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 AD risk genes alter 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 proposal his team will apply
these methods to the study of early genetic 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 structural 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 that are attributable to AD-related genes. For these Aims, Dr.
Warren will develop a new dataset from a large sample (N=184) of healthy youths aged 9, 12, or 15 years-old
that combines neuroimaging (brain structure/function), neuropsychological tests (cognition), and genomic
assays (AD-related genes) in a cross-sectional design. Dr. Warren’s team will analyze these data to better
understand the pressing clinical problem of AD from a devel...

## Key facts

- **NIH application ID:** 9856131
- **Project number:** 1P20GM130447-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** David E Warren
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,128
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856131

## Citation

> US National Institutes of Health, RePORTER application 9856131, Quantifying neurodevelopmental effects of polygenic risk for Alzheimer's disease via cross-sectional study of brain and cognition in periadolescent children (1P20GM130447-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9856131. Licensed CC0.

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