The Brains of Infants With Alzheimer Gene
Dean DC 3rd, Jerskey BA, Chen K, et al
JAMA Neurol. 2013 Nov 25. [Epub ahead of print]
Research findings in Alzheimer disease (AD) suggest that changes in brain structure may precede clinical cognitive impairment by several decades. Early recognition of these changes could help identify persons at risk and facilitate development and assessment of preventive strategies.
The aim of this study was to compare MRI measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, which is the major gene determining susceptibility to late-onset AD.
At an academic research imaging center, 162 healthy 2- to 25-month-old infants with apparently normal development and no family history of AD or other neurologic or psychiatric disorders underwent quiet MRI while they were sleeping. Using automated algorithms, the investigators compared cross-sectional measurements of white matter MWF in carriers (n = 60) and noncarriers (n = 102) of APOE ε4.
During scanning, 23 ε4 carriers and 36 noncarriers remained asleep long enough for measurement of GMV, allowing between-group comparisons. Age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status were similar in the carrier and noncarrier groups.
Compared with noncarriers of ε4, carriers had lower MWF and GMV measurements in areas preferentially affected by AD, including the precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, and greater MWF and GMV measurements in extensive frontal regions. The difference in MWF between carriers and noncarriers was also significant in the subset of 2- to 6-month-old infants. The relationship between MWF and age was attenuated in posterior white matter regions among infant ε4 carriers.
Limitations of this study include its cross-sectional design and the loss of significance in reported regional GMV changes after statistical correction for multiple comparisons. These preliminary findings should therefore be confirmed in subsequent longitudinal studies. Nonetheless, this study shows some of the earliest brain changes demonstrated thus far among infants with a genetic predisposition to AD. The findings of this study suggest that APOE may be implicated in normal human brain development. In fact, the APOE protein is known to participate in the transport and clearance of cholesterol, which could affect the development, maintenance, and repair of synapses and myelinated neurons. This potential pathway underlying subsequent AD pathology may be a target for interventions designed to prevent AD.
Abstract
Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease: A Cross-sectional Imaging Study
Dean DC 3rd, Jerskey BA, Chen K, et al
JAMA Neurol. 2013 Nov 25. [Epub ahead of print]
Study Summary
Research findings in Alzheimer disease (AD) suggest that changes in brain structure may precede clinical cognitive impairment by several decades. Early recognition of these changes could help identify persons at risk and facilitate development and assessment of preventive strategies.
The aim of this study was to compare MRI measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, which is the major gene determining susceptibility to late-onset AD.
At an academic research imaging center, 162 healthy 2- to 25-month-old infants with apparently normal development and no family history of AD or other neurologic or psychiatric disorders underwent quiet MRI while they were sleeping. Using automated algorithms, the investigators compared cross-sectional measurements of white matter MWF in carriers (n = 60) and noncarriers (n = 102) of APOE ε4.
During scanning, 23 ε4 carriers and 36 noncarriers remained asleep long enough for measurement of GMV, allowing between-group comparisons. Age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status were similar in the carrier and noncarrier groups.
Compared with noncarriers of ε4, carriers had lower MWF and GMV measurements in areas preferentially affected by AD, including the precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, and greater MWF and GMV measurements in extensive frontal regions. The difference in MWF between carriers and noncarriers was also significant in the subset of 2- to 6-month-old infants. The relationship between MWF and age was attenuated in posterior white matter regions among infant ε4 carriers.
Viewpoint
Limitations of this study include its cross-sectional design and the loss of significance in reported regional GMV changes after statistical correction for multiple comparisons. These preliminary findings should therefore be confirmed in subsequent longitudinal studies. Nonetheless, this study shows some of the earliest brain changes demonstrated thus far among infants with a genetic predisposition to AD. The findings of this study suggest that APOE may be implicated in normal human brain development. In fact, the APOE protein is known to participate in the transport and clearance of cholesterol, which could affect the development, maintenance, and repair of synapses and myelinated neurons. This potential pathway underlying subsequent AD pathology may be a target for interventions designed to prevent AD.
Abstract
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