# Influence of APOE4 Genotype on Neonatal Cortical Morphology

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2020 · $422,432

## Abstract

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer’s disease (AD).
While there is growing evidence that APOE affects early life brain development, an exact quantification of the
extent of this effect is unknown. We propose to develop a complete morphometric analysis of cortical grey
matter (cGM) from neonatal MRI, and to use these tools quantify the difference in brain between term and pre-
term APOE4 carriers and non-carriers to assess whether the deficit due to APOE4 is significantly higher in
preterm as compared to term neonates. Our laboratories combine expertise in shape analysis of brain
structures using MRI, and we have designed numerous tools for this purpose, particularly in pediatrics. In the
parent version of this supplement, we are using some of these tools for the comparison of subcortical
structures in preterm vs. term neonates, and to study associated long-term outcomes. In fall 2019, we also
obtained a supplement for this R01 titled: “Effects of genetic and gestational risk factors for late onset
Alzheimer's disease on neonatal brain morphology”, for which we are calling back preterm and term subjects
0-18 years old who obtained an MRI at neonatal ages. We are determining ApoE status on these subjects
through saliva collection, and then using this information in conjunction with their neonatal scans to study how
hippocampal morphology is affected by ApoE and prematurity statuses. However, the cortex is also known to
be affected in both prematurity and Alzheimer’s disease. Hence, here we will build on our prior supplement and
use this dataset to determine cortical morphology in these populations. First, we will extend our methods in two
ways: (1) Current online segmentation methods require 20-40 hours of subsequent expert manual editing. We
will build a new geodesic transform based infant brain cortical segmentation. Our preliminary work has shown
great success in improving manual correction times. (2) Additionally, we will use our multivariate tensor-based
morphometry (mTBM) algorithm that measures local cortical area changes, combined with a new
morphometric Gaussian process (M-GP) latent cortical thickness landmark selection method to powerfully
determine cortical differences between preterm and term-born neonates based on their ApoE status. Our
descriptions of normal development may be used as normative comparison values for neurodevelopmental
pathologies, which may lead to earlier detection and optimized treatment. The software developed here will be
made available to the research community. Secondly, these tools will be used to obtain a complete picture of
the differences in cortical growth between APOE4 carriers and non-carriers. In addition to being a risk factor for
AD, APOE4 carriers tend to get worse outcomes in conditions such as traumatic brain injury, chemotherapy
induced brain damage, hypoalphalipoproteinemia and cardiovascular disease, among others. When children
are affect...

## Key facts

- **NIH application ID:** 10123955
- **Project number:** 3R01EB025032-04S1
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Natasha Lepore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,432
- **Award type:** 3
- **Project period:** 2017-09-22 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123955

## Citation

> US National Institutes of Health, RePORTER application 10123955, Influence of APOE4 Genotype on Neonatal Cortical Morphology (3R01EB025032-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123955. Licensed CC0.

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