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Differences in temporal AD biomarker trajectories according to sex and APOE genotype: Implication of importance of striatal amyloid
Author(s) -
Chun Min Young,
Kim Jun Pyo,
Kim SooJong,
Jang Hyemin,
Kim Hee Jin,
Na Duk L.,
Seo Sang Won
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.057641
Subject(s) - positron emission tomography , apolipoprotein e , biomarker , standardized uptake value , medicine , psychology , nuclear medicine , neuroscience , oncology , pathology , disease , chemistry , biochemistry
Background Accumulation of β‐amyloid (Aβ) plaques and neurofibrillary tangles are core components of Alzheimer's disease (AD) pathogenesis. Longitudinal in vivo observations of AD pathologic changes using amyloid and tau positron emission tomography (PET) enable us to obtain AD biomarkers' hypothetical trajectory curves. However, the difference in disease progression by striatal Aβ deposition, sex, and apolipoprotein E (APOE) genotype has not been explained with trajectory curves. The aim of this study is to develop the trajectory in accumulation of cortical and striatal Aβ and tau deposits. We also tried to investigate the differences in sex and APOE genotype on trajectory curves. Method We obtained 817 subjects from the Alzheimer’s Disease Neuroimaging Initiative database, who showed either 18 F‐florbetapir (AV45) PET positivity at least once or AV45 PET negativity with normal cognition. We Z‐transformed each value based on Aβ‐negative, cognitively normal subjects. Instead of obtaining a single rate value (∆Z/∆t) per subject, we calculated the slope for every interval of PET scans. For each biomarker, we fitted a penalized spline to model the slope of Z value as a nonlinear function of baseline Z value. Using the fitted splines, we obtained the predicted Z curves as a function of time and developed trajectory curves. Result Among the subjects, 534 subjects were available for AV45 PET analysis and 163 subjects underwent 18 F‐flortaucipir PET. While cortical Aβ accumulation rate increased until Z value reached 4.33 and decreased subsequently, ∆Z/∆t for the striatal Aβ and tau stayed more constant. Time from Z=0 to Z=2 was the longest for tau PET (22.6 years) and shortest for cortical Aβ (14.9 years). For cortical Aβ, Z values of males reached 1.7 years earlier than females. However, for striatal Aβ, males took 2.8 more years than females to reach Z=2. Also, APOE ɛ4 carriers showed faster progression for all biomarkers. Conclusion This study shows that Aβ accumulates in the striatum after cortex and then tau protein, which is consistent with the amyloid cascade hypothesis. The trajectory curves differ according to sex and APOE genotype. Therefore, prognosis and treatment should be approached differently in clinical practice with respect to striatal involvement, sex, and APOE genotype.