Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease

Sylvia Villeneuve, Jacob W. Vogel, Julie Gonneaud, Alexa Pichet Binette, Pedro Rosa-Neto, Serge Gauthier, Randall J. Bateman, Anne M. Fagan, John C. Morris, Tammie L. S. Benzinger, Sterling C. Johnson, John C. S. Breitner, Judes Poirier, Alan Barkun, Alan Evans, Alyssa Salaciak, Angela Tam, Anne Labonté, Anne-Marie Faubert, Axel MathieuBlandine Courcot, Bradley T. Hyman, C. cile Madjar, Charles Edouard Carrier, Christian Dansereau, Christina Kazazian, Christine Tardif, Claude Lepage, Claudio Cuello, Clément Debacker, Clifford R. Jack, Cynthia Picard, David Maillet, David Fontaine, David S. Knopman, Diane Michaud, Doris Couture, Doris Dea, Eduard Teigner, Elena Anthal, Elsa Yu, Etienne Vachon-Presseau, Eunice Farah Saint-Fort, Fabiola Ferdinand, Fatiha Benbouhoud, Galina Pogossova, Gerhard Maultaup, Ginette Mayrand, Guerda Duclair, Sander C. J. Verfaillie, Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group

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Abstract

IMPORTANCE Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. OBJECTIVE To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information about amyloid-β (Aβ) levels in asymptomatic individuals with a parental history of AD dementia. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed Aβ1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively normal individuals who had a lumbar puncture as part of the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort from September 1, 2011, through November 30, 2016 (374 participants were enrolled in the cohort during this period). The study estimated each participant's proximity to his/her parent's symptom onset by subtracting the index relative's onset age from his/her current age. The association between proximity to parental symptom onset and Aβ levels was then assessed using apolipoprotein E ϵ4 (APOE4) status and sex as interactive terms. These analyses were performed again in 2 independent cohorts using CSF and Pittsburgh compound B carbon 11-labeled positron emission tomography (PIB-PET) Aβ biomarkers: the Adult Children Study (ACS) and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts. MAIN OUTCOMES AND MEASURES The association between proximity to parental symptom onset and Aβ burden in asymptomatic individuals with a parental history of sporadic AD. RESULTS The present analysis included a subset of 101 PREVENT-AD individuals (mean [SD] age, 61.8 [5.1] years; 30 [29.7%] male), 128 ACS participants (112 participants underwent CSF measurement: mean [SD] age, 63.4 [5.1] years; 31 [27.7%] male; and 107 underwent PIB-PET: mean [SD] age, 64.6 [5.3] years; 27 [25.2%] male), and 135 WRAP participants (85 participants underwent CSF measurement: mean [SD] age, 59.9 [6.0] years; 27 [31.8%] male; and 135 underwent PIB-PET: mean [SD] age, 59.6 [6.1] years; 43 [31.9%] male). In the PREVENT-AD cohort, individuals approaching their parent's onset age had lower CSF Aβ1-42 levels (range, 402-1597; B = -9.09, P = .04). This association was stronger in APOE4 carriers (B = -17.9, P = .03) and women (B = -19.8, P = .02). In the ACS cohort, the main association was replicated using PIB-PET data, and the sex interaction was replicated using CSF and PIB-PET data. In the WRAP cohort, the results were not replicated using cross-sectional data, but the main association and the APOE interaction were replicated using PIB-PET longitudinal data. CONCLUSIONS AND RELEVANCE These results suggest that proximity to parental symptom onsetmay help estimate Aβ biomarker changes in women or APOE4 carrier asymptomatic individuals with a parental history of sporadic AD.
Original languageEnglish
Pages (from-to)608-619
JournalJAMA Neurology
Volume75
Issue number5
DOIs
Publication statusPublished - 2018

Cite this

Villeneuve, S., Vogel, J. W., Gonneaud, J., Pichet Binette, A., Rosa-Neto, P., Gauthier, S., ... Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) Research Group (2018). Proximity to parental symptom onset and amyloid-β burden in sporadic Alzheimer disease. JAMA Neurology, 75(5), 608-619. https://doi.org/10.1001/jamaneurol.2017.5135