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Abstract
Objective To determine whether years of education and the ε4 risk allele at APOE influence β-amyloid (Aβ) pathology similarly in asymptomatic individuals with a family history of sporadic Alzheimer disease (AD) and presymptomatic autosomal dominant AD mutation carriers.
Methods We analyzed cross-sectional data from 106 asymptomatic individuals with a parental history of sporadic AD (PREVENT-AD cohort; age 67.28 ± 4.72 years) and 117 presymptomatic autosomal dominant AD mutation carriers (DIAN cohort; age 35.04 ± 9.43 years). All participants underwent structural MRI and Aβ-PET imaging. In each cohort we investigated the influence of years of education, APOE ε4 status, and their interaction on Aβ-PET.
Results Asymptomatic individuals with a parental history of sporadic AD showed increased Aβ burden associated with APOE ε4 carriage and lower level of education, but no interaction between these. Presymptomatic mutation carriers of autosomal dominant AD showed no relation between APOE ε4 and Aβ burden, but increasing level of education was associated with reduced Aβ burden. The association between educational attainment and Aβ burden was similar in the 2 cohorts.
Conclusions While the APOE ε4 allele confers increased tendency toward Aβ accumulation in sporadic AD only, protective environmental factors, like increased education, may promote brain resistance against Aβ pathology in both sporadic and autosomal dominant AD.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADAD=
- autosomal dominant Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- CDR=
- Clinical Dementia Rating;
- DIAN=
- Dominantly Inherited Alzheimer Network;
- EYO=
- expected years to symptom onset;
- GAAIN=
- Global Alzheimer's Association Interactive Network;
- GLM=
- general linear model;
- MMSE=
- Mini-Mental State Examination;
- MNI=
- Montreal Neurological Institute;
- pEYO=
- parental expected years to symptom onset;
- PiB=
- Pittsburgh compound B;
- PREVENT-AD=
- Presymptomatic Evaluation of Experimental or Novel Treatments for AD;
- sAD=
- sporadic Alzheimer disease;
- SUVR=
- standardized uptake value ratio;
- VOI=
- volume of interest
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
PREVENT-AD Research Group and DIAN Study Group coinvestigators are listed at links.lww.com/WNL/B169.
Data used in preparation of this article were obtained from the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) program (douglas.research.mcgill.ca/stop-ad-centre), data release 5.0 (November 30, 2017). A complete listing of PREVENT-AD Research Group members can be found in the online data supplement and in the PREVENT-AD database: preventad.loris.ca/acknowledgements/acknowledgements.php?date=[2018-04-30].
- Received July 2, 2019.
- Accepted in final form March 23, 2020.
- © 2020 American Academy of Neurology
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