The Alzheimer's Prevention Initiative Autosomal‐Dominant Alzheimer's Disease Trial: A study of crenezumab versus placebo in preclinical <i>PSEN1</i> E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal‐dominant Alzheimer's disease, including a placebo‐treated noncarrier cohort

Tariot, Pierre N.; Lopera, Francisco; Langbaum, Jessica B.; Thomas, Ronald G.; Hendrix, Suzanne; Schneider, Lon S.; Ríos‐Romenets, Silvia; Giraldo, Margarita; Acosta, Natalia; Tobón, Carlos; Ramos, Cláudia; Espinosa, Alejandro; Cho, William; Ward, Michael E.; Clayton, David; Friesenhahn, Michael; Mackey, Howard M.; Honigberg, Lee; Bohórquez, Sandra Sanabria; Chen, Kewei; Walsh, Trisha; Langlois, Carolyn; Reiman, Eric M.; Initiative, Alzheimer's Prevention

doi:10.1016/j.trci.2018.02.002

Cited by 115 publications

(105 citation statements)

References 57 publications

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“…One study further reported a significant race by APOE 4 interaction for both CSF t-tau and p-tau, 12 suggesting that the racial disparities in these biomarkers, and hence in the more downstream clinical changes, may depend on APOE 4 status, consistent with our current findings. Specifically, both biomarker studies 11,12 Inherited Alzheimer Network (DIAN) trials, 33 and the Alzheimer's Prevention Initiative (API) trial 34 are ongoing. Primary prevention trials are currently planned.…”

Section: Discussionmentioning

confidence: 99%

Complex interactions underlie racial disparity in the risk of developing Alzheimer's disease dementia

Xiong

Luo

Coble

et al. 2020

Alzheimer's & Dementia

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Introduction We aim to determine racial disparities and their modifying factors in risk for Alzheimer's disease (AD) dementia among cognitively normal individuals 65 years or older. Methods Longitudinal data from the National Alzheimer's Coordinating Center Uniform Data Set on 1229 African Americans (AAs) and 6679 whites were analyzed for the risk of AD using competing risk models with death as a competing event. Results Major AD risk factors modified racial differences which, when statistically significant, occurred only with older age among APOE ε4 negative individuals, but also with younger age among APOE ε4 positive individuals. The racial differences favored AAs among individuals with body mass index (BMI) < 30, but whites among individuals with a high BMI (≥ 30), and were additionally modified by sex, education, hypertension, and smoking status. Conclusions The presence, direction, and relative magnitude of racial disparity for AD represent an interactive function of major AD and cerebrovascular risk factors.

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Section: Discussionmentioning

confidence: 99%

Complex interactions underlie racial disparity in the risk of developing Alzheimer's disease dementia

Xiong

Luo

Coble

et al. 2020

Alzheimer's & Dementia

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“…Over 1,800 Colombian PSEN1 E280A carriers and 4,000 non-carrier family members who trace their lineage back to a single-common ancestor with the mutation participate in research at the University of Antioquia and collaborating sites in the United States [11]. As research in this cohort progresses – including a five-year phase 2 clinical trial of the anti-amyloid agent Crenezumab involving 300 Colombian kindred members, 200 of whom are mutation carriers [12] – a review that unifies our understanding of the PSEN1 E280A literature is needed.…”

Section: Introductionmentioning

confidence: 99%

Biological and Cognitive Markers of Presenilin1 E280a Autosomal Dominant Alzheimer’s Disease: A Comprehensive Review of the Colombian Kindred

et al. 2019

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The study of individuals with autosomal dominant Alzheimer’s disease affords one of the best opportunities to characterize the biological and cognitive changes of Alzheimer’s disease that occur over the course of the preclinical and symptomatic stages. Unifying the knowledge gained from the past three decades of research in the world’s largest single-mutation autosomal dominant Alzheimer’s disease kindred — a family in Antioquia, Colombia with the E280A mutation in the Presenilin1 gene — will provide new directions for Alzheimer’s research and a framework for generalizing the findings from this cohort to the more common sporadic form of Alzheimer’s disease. As this specific mutation is virtually 100% penetrant for the development of the disease by midlife, we use a previously defined median age of onset for mild cognitive impairment for this cohort to examine the trajectory of the biological and cognitive markers of the disease as a function of the carriers’ estimated years to clinical onset. Studies from this cohort suggest that structural and functional brain abnormalities — such as cortical thinning and hyperactivation in memory networks — as well as differences in biofluid and in vivo measurements of Alzheimer’s-related pathological proteins distinguish Presenilin1 E280A mutation carriers from non-carriers as early as childhood, or approximately three decades before the median age of onset of clinical symptoms. We conclude our review with discussion on future directions for Alzheimer’s disease research, with specific emphasis on ways to design studies that compare the generalizability of research in autosomal dominant Alzheimer’s disease to the larger sporadic Alzheimer’s disease population.

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“…The Alzheimer's Prevention Initiative (API), established in 2010, is a collaborative research program led by Banner Alzheimer's Institute in partnership with other key organizations working to accelerate the evaluation of interventions to prevent AD dementia [4,8]. In 2012, API received a National Institutes of Health (NIH) grant to help support the Colombia Autosomal Dominant AD Trial (ctgov:NCT01998841), the first funded prevention trial of an investigational disease‐modifying treatment in cognitively unimpaired mutation carriers and noncarriers from the world's largest autosomal dominant AD kindred.…”

Section: Introductionmentioning

confidence: 99%

“…In 2012, API received a National Institutes of Health (NIH) grant to help support the Colombia Autosomal Dominant AD Trial (ctgov:NCT01998841), the first funded prevention trial of an investigational disease‐modifying treatment in cognitively unimpaired mutation carriers and noncarriers from the world's largest autosomal dominant AD kindred. Because many kindred members do not want to know their genetic status and there was no established paradigm for genetic disclosure in Colombia, this ongoing study includes both mutation carriers who are randomized to active treatment or placebo and noncarriers who receive placebo, and it does not include genetic disclosure [4].…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's Prevention Initiative Generation Program: Development of an APOE genetic counseling and disclosure process in the context of clinical trials

Langlois¹,

Bradbury

Wood

et al. 2019

A&D Transl Res & Clin Interv

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Introduction As the number of Alzheimer's disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E (APOE) results efficiently, safely, and effectively in the context of AD prevention trials. Methods A multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer's Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials. Results The Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact. Discussion The API Genetic Counseling and Disclosure Process provides a framework for large‐scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological well‐being before and after APOE disclosure are still being collected and will be presented in a future publication.

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Cited by 115 publications

References 57 publications

Complex interactions underlie racial disparity in the risk of developing Alzheimer's disease dementia

Complex interactions underlie racial disparity in the risk of developing Alzheimer's disease dementia

Biological and Cognitive Markers of Presenilin1 E280a Autosomal Dominant Alzheimer’s Disease: A Comprehensive Review of the Colombian Kindred

Alzheimer's Prevention Initiative Generation Program: Development of an APOE genetic counseling and disclosure process in the context of clinical trials

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