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Title
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APOE effect on amyloid- PET spatial distribution, deposition rate, and cut-points
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Author
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Institution/Organisation
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Alzheimers Dis Neuroimaging Initia
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Abstract
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| There are conflicting results regarding how APOE genotype, the strongest genetic risk factor for Alzheimer's disease (AD), influences spatial and longitudinal amyloid-beta (A beta) deposition and its impact on the selection of biomarker cut-points. In our study, we sought to determine the impact of APOE genotype on cross-sectional and longitudinal florbetapir positron emission tomography (PET) amyloid measures and its impact in classification of patients and interpretation of clinical cohort results. We included 1,019 and 1,072 Alzheimer's Disease Neuroimaging Initiative participants with cerebrospinal fluid A beta 1 - 42 and florbetapir PET values, respectively. 623 of these subjects had a second florbetapir PET scans two years after the baseline visit. We evaluated the effect of APOE genotype on A beta distribution pattern, pathological biomarker cut-points, cross-sectional clinical associations with A beta load, and longitudinal A beta deposition rate measured using florbetapir PET scans. 1) APOE epsilon 4 genotype influences brain amyloid deposition pattern; 2) APOE epsilon 4 genotype does not modify A beta biomarker cut-points estimated using unsupervised mixture modeling methods if white matter and brainstem references are used (but not when cerebellum is used as a reference); 3) findings of large differences in A beta biomarker value differences based on APOE genotype are due to increased probability of having AD neuropathology and are most significant in mild cognitive impairment subjects; and 4) APOE genotype and age (but not gender) were associated with increased A beta deposition rate. APOE epsilon 4 carrier status affects rate and location of brain A beta deposition but does not affect choice of biomarker cut-points if adequate references are selected for florbetapir PET processing. |
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Language
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English
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Source (journal)
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Journal of Alzheimer's disease. - -
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Publication
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2019
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ISSN
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1387-2877
1875-8908
[Electronic]
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DOI
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10.3233/JAD-181282
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Volume/pages
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69
:3
(2019)
, p. 783-793
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ISI
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000471781600015
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Pubmed ID
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31127775
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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