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Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load
Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load
- Source :
- Neurology 88(6), 569-576 (2017). doi:10.1212/WNL.0000000000003585
- Publication Year :
- 2016
-
Abstract
- Objective:To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach.Methods:Multimodal neuroimaging data were obtained from a total of 572 older individuals without dementia (cognitively normal and mild cognitive impairment) enrolled in the Alzheimer's Disease Neuroimaging Initiative and included assessments of regional amyloid load with AV45-PET, glucose metabolism with fluorodeoxyglucose-PET, and gray matter volume with structural MRI. Imaging indexes of APOE2 carriers were contrasted to risk-neutral APOE3 homozygotes, and analyses were controlled for age, sex, education, and clinical diagnosis. Additional models examined genotype-specific effects of age on the imaging markers.Results:In region-of-interest–based analyses, APOE2 carriers had significantly less precuneal amyloid pathology and did not show the typical age-related increase in amyloid load, although the age × genotype interaction was only trend-level significant. In contrast, parietal metabolism and hippocampal volume did not differ between APOE2 and APOE3 genotypes, and both groups showed comparable negative effects of age on these markers. The amyloid specificity of APOE2-related brain changes was corroborated in 2 complementary analyses: spatially unbiased voxel-wise analyses showing widespread reductions in amyloid deposition but no differences in gray matter volume or metabolism and an analysis of CSF-based biomarkers showing a significant effect on amyloid but not on tau pathology.Conclusions:Regarding the range of Alzheimer disease biomarkers considered in the present study, the APOE2 allele appears to have a relatively selective effect on reduced accumulation of amyloid pathology in the aged brain.
- Subjects :
- 0301 basic medicine
Oncology
Male
Aging
Apolipoprotein E2
diagnostic imaging [Cognitive Dysfunction]
Apolipoprotein E3
metabolism [Gray Matter]
Disease
Multimodal Imaging
metabolism [Cognitive Dysfunction]
pathology [Aging]
0302 clinical medicine
Genotype
Medicine
Gray Matter
medicine.diagnostic_test
Brain
Organ Size
Magnetic Resonance Imaging
metabolism [Glucose]
cerebrospinal fluid [Biomarkers]
Positron emission tomography
genetics [Aging]
genetics [Apolipoprotein E3]
Female
Alzheimer's disease
medicine.medical_specialty
Amyloid
Heterozygote
Neuroimaging
Article
03 medical and health sciences
Fluorodeoxyglucose F18
Internal medicine
genetics [Apolipoprotein E2]
Dementia
Humans
Cognitive Dysfunction
ddc:610
metabolism [Aging]
Allele
diagnostic imaging [Brain]
metabolism [Amyloid]
Aged
business.industry
diagnostic imaging [Gray Matter]
Magnetic resonance imaging
medicine.disease
030104 developmental biology
Glucose
metabolism [Brain]
Positron-Emission Tomography
Neurology (clinical)
Radiopharmaceuticals
business
030217 neurology & neurosurgery
Biomarkers
Subjects
Details
- ISSN :
- 1526632X
- Volume :
- 88
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Neurology
- Accession number :
- edsair.doi.dedup.....b2e14f62236fbe531ce6e56e372f4183
- Full Text :
- https://doi.org/10.1212/WNL.0000000000003585