Influence of apolipoprotein-E genotype on brain amyloid load and longitudinal trajectories

NEUROBIOLOGY OF AGING

卷:94

Article

Lopresti, Brian J.¹  Campbell, Elizabeth M.¹  Yu, Zheming¹  Anderson, Stewart J.²  Cohen, Ann D.³  Minhas, Davneet S.¹  Snitz, Beth E.⁴  Royse, Sarah K.¹  Becker, Carl R.¹  Aizenstein, Howard J.³  Mathis, Chester A.¹  Lopez, Oscar L.⁴  Klunk, William E.³  Tudorascu, Dana L.^2,3 

[1] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA

[2] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA

[4] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA

关键词: Alzheimer's disease;    Apolipoprotein-E;    Positron emission tomography (PET);    Amyloid;    Genetics;   

DOI  :  10.1016/j.neurobiolaging.2020.05.012

来源: Elsevier

【 摘 要 】

To characterize the influence of apolipoprotein-E (APOE) genotype on cerebral A beta load and longitudinal A beta trajectories, [C-11]Pittsburgh compound-B (PiB) positron emission tomography (PET) imaging was used to assess amyloid load in a clinically heterogeneous cohort of 428 elderly participants with known APOE genotype. Serial [C-11 epsilon]PiB data and a repeated measures model were used to model amyloid trajectories in a subset of 235 participants classified on the basis of APOE genotype. We found that APOE-epsilon 4 was associated with increased A beta burden and an earlier age of onset of A beta positivity, whereas APOE-epsilon 2 appeared to have modest protective effects against A beta. APOE class did not predict rates of A beta accumulation. The present study suggests that APOE modifies Alzheimer's disease risk through a direct influence on amyloidogenic processes, which manifests as an earlier age of onset of A beta positivity, although it is likely that other genetic, environmental, and lifestyle factors are important. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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