Variation in Neurodegeneration-Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida

Annals of the Child Neurology Society Pub Date : 2025-07-03 DOI:10.1002/cns3.70016

Joan M. Jasien, Jacques A. Stout, Mohamad A. Mikati, Robert J. Anderson, Brittany G. Nave, Herbert E. Fuchs, Brian Smith, Alexandra Badea, Jeffrey N. Browndyke

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Abstract

Objective

Possible pleiotropic effects of apolipoprotein E4 (APOE E4) in individuals with congenital brain malformations are relatively unknown. Our goal was to determine if neurodegeneration-linked brain region volumes differ significantly between E4 carriers and noncarriers in young adults with spina bifida (SB).

Methods

Eleven individuals ( > 18 years), genotyped for APOE, underwent neuroimaging and neurocognitive evaluation. Primary analysis: Magnetic resonance imaging (MRI) data from 10 a priori neurodegeneration-risk regions of interest were compared between E4 carriers and noncarriers, adjusting for age, sex, and total intracranial volume (FDR-adjusted p < 0.05). Secondary analyses: Age-adjusted neurocognitive standard scores were compared between groups (p < 0.05). Post hoc analyses of NeuroQuant-derived regional brain volumes were examined for combined group differences in young adults with SB.

Results

Comparison of a priori risk region volumes revealed significantly lower left amygdala volumes (FDR-adjusted p = 0.04) in young adult E4 carriers (n = 4) relative to noncarriers (n = 7). Neurocognitive data were not significantly different between the groups. A possible trend was detected for enlarged parietal volumes in E4 carriers (p = 0.07), while volumetric extremes ( > 95% or < 5%) were detected for the anterior cingulate (100% of cases; p = 0.001), frontal cortices (90% of cases), hippocampus (80% of cases), and entorhinal cortices (70% of cases).

Interpretation

Early left amygdala volumetric reduction was found in E4 carriers; combined group volume comparisons revealed frontal and temporal lobe differences in young adults with SB relative to age- and sex-matched volumetric estimates. This pilot investigation does not appear to support E4 conferring a pleiotropic benefit in young adults with SB but rather supports further investigation of MRI volumetrics as a possible biomarker for this population.

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年轻成人脊柱裂APOE E4携带者神经变性相关脑区变异

目的载脂蛋白E4 （APOE E4）在先天性脑畸形患者中可能的多效性作用尚不清楚。我们的目的是确定患有脊柱裂（SB）的年轻成人中E4携带者和非携带者的神经变性相关脑区体积是否有显著差异。方法11例（18岁）APOE基因分型患者行神经影像学和神经认知评价。主要分析：比较E4携带者和非携带者的10个先验神经变性危险区域的磁共振成像（MRI）数据，调整年龄、性别和颅内总容积（经fdr校正p <； 0.05）。二次分析：组间年龄校正神经认知标准评分比较（p < 0.05）。对神经定量衍生的区域脑容量进行事后分析，研究了年轻成人SB患者的联合组差异。结果比较先验风险区域容量显示，年轻成人E4携带者（n = 4）的左杏仁核体积（fdr调整p = 0.04）明显低于非携带者（n = 7）。两组间神经认知数据无显著差异。E4携带者的顶叶体积增大可能是一种趋势（p = 0.07），而前扣带（100%的病例；p = 0.001）、额皮质（90%的病例）、海马（80%的病例）和内嗅皮质（70%的病例）的体积极值（>； 95%或<； 5%）被检测到。E4携带者早期左侧杏仁核体积减小；联合组体积比较显示，相对于年龄和性别匹配的体积估计，年轻SB患者的额叶和颞叶存在差异。这项试点研究似乎不支持E4对年轻SB患者具有多效性益处，而是支持进一步研究MRI体积作为该人群的可能生物标志物。

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Annals of the Child Neurology Society

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