APOE ε4 genotype, amyloid-β, and sex interact to predict tau in regions of high APOE mRNA expression.

Autor: Dincer A; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Chen CD; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., McKay NS; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Koenig LN; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., McCullough A; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Flores S; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Keefe SJ; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Schultz SA; Massachusetts General Hospital, Boston, MA 02114, USA., Feldman RL; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Joseph-Mathurin N; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Hornbeck RC; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Cruchaga C; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA., Schindler SE; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Holtzman DM; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO 63110, USA., Morris JC; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Fagan AM; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Benzinger TLS; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA., Gordon BA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Psychological and Brain Sciences, Washington University, Saint Louis, MO 63110, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2022 Nov 16; Vol. 14 (671), pp. eabl7646. Date of Electronic Publication: 2022 Nov 16.
DOI: 10.1126/scitranslmed.abl7646
Abstrakt: The apolipoprotein E ( APOE ) ε4 allele is strongly linked with cerebral β-amyloidosis, but its relationship with tauopathy is less established. We investigated the relationship between APOE ε4 carrier status, regional amyloid-β (Aβ), magnetic resonance imaging (MRI) volumetrics, tau positron emission tomography (PET), APOE messenger RNA (mRNA) expression maps, and cerebrospinal fluid phosphorylated tau (CSF ptau 181 ). Three hundred fifty participants underwent imaging, and 270 had ptau 181 . We used computational models to evaluate the main effect of APOE ε4 carrier status on regional neuroimaging values and then the interaction of ε4 status and global Aβ on regional tau PET and brain volumes as well as CSF ptau 181 . Separately, we also examined the additional interactive influence of sex. We found that, for the same degree of Aβ burden, APOE ε4 carriers showed greater tau PET signal relative to noncarriers in temporal regions, but no interaction was present for MRI volumes or CSF ptau 181 . This potentiation of tau aggregation irrespective of sex occurred in brain regions with high APOE mRNA expression, suggesting local vulnerabilities to tauopathy. There were greater effects of APOE genotype in females, although the interactive sex effects did not strongly mirror mRNA expression. Pathology is not homogeneously expressed throughout the brain but mirrors underlying biological patterns such as gene expression.
Databáze: MEDLINE
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