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Neurobiol Aging. 2019 Mar;75:42-50. doi: 10.1016/j.neurobiolaging.2018.10.011. Epub 2018 Oct 13.

Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network.

Author information

1
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
2
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Department of Neurology, Washington University School of Medicine, Saint Louis, MO. Electronic address: sniderj@wustl.edu.
3
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO.
4
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO.
5
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Department of Radiology, Washington University School of Medicine, Saint Louis, MO.

Abstract

The apolipoprotein E ε4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD. We analyzed the effect of an APOE4 allele on cognitive measures, volumetric MRI, amyloid deposition, glucose metabolism, and on cerebrospinal fluid levels of AD biomarkers in 162 participants that did not carry the mutant gene (noncarriers). APOE4+ and APOE4- mutation noncarriers had similar performance on cognitive measures. Amyloid deposition began at an earlier age in APOE4+ participants, whereas hippocampal volume was similar between the groups. These preliminary findings are consistent with growing evidence that the APOE4 allele may exert effects in midlife years before symptom onset, promoting amyloid deposition before altering cognitive performance or brain structure.

KEYWORDS:

APOE; Alzheimer disease; Amyloid precursor protein; Autosomal dominant; Biomarkers; Presenilin 1; Presenilin 2

PMID:
30530186
PMCID:
PMC6385602
[Available on 2020-03-01]
DOI:
10.1016/j.neurobiolaging.2018.10.011
[Indexed for MEDLINE]

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