Investigators at Brown University, Providence, RI, and other imaging genetic centers in the US, 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) e4 allele, the major susceptibility gene for late-onset Alzheimer disease (AD). Infant e4 carriers, ages 2–25 months, had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas affected by AD, whereas these measures were greater in frontal regions, and an attenuated relationship between MWF and age was evident in posterior white matter regions. The study demonstrates some of the earliest brain changes associated with a genetic predisposition to AD, and the role of APOE in normal human brain development and AD pathology. 
COMMENTARY. In a comment (Alzheimer gene APOE e4 linked to brain development in infants), Drs McDonald and Krainc of Northwestern University Feinberg School of Medicine find that this study highlights compelling evidence of the influence of the APOE e4 allele on brain structure in young infants. It remains to be determined whether these neurodevelopmental observations specifically influence AD pathogenesis in later life . In an editorial, Growdon JH, and Hyman BT allude to data emphasizing effects of B-amyloid on neural plasticity during brain development, a peptide elevated in Down syndrome where trisomy 21 leads to an extra copy of the amyloid precursor protein and early onset AZ .
A study of effect of age and APOE genotype on neuropathological changes in Down syndrome hippocampal formation found that individuals who had inherited the APOE e4 genotype contained more than twice the amyloid burden of non-carriers. The level of amyloid deposition in Down syndrome patients is higher than in sporadic AZ disease . Inheritance of the APOE e4 genotype is an independent risk factor for developing higher levels of amyloid accumulation.