Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease

Aschenbrenner, Andrew J.; Baksh, R. Asaad; Benejam, Bessy; Beresford‐Webb, Jessica; Coppus, Antonia; Fortea, Juan; Handen, Benjamin L.; Hartley, Sigan L.; Head, Elizabeth; Jaeger, Judith; Levin, Johannes; Loosli, Sandra; Rebillat, Anne Sophie; Sacco, Silvia; Schmitt, Frederick A.; Thurlow, Katherine E.; Zaman, Shahid; Hassenstab, Jason; Strydom, André

doi:10.1002/dad2.12184

Cited by 14 publications

(31 citation statements)

References 35 publications

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“…14,17,58 Accordingly, our findings distinguishing DS and AD-DS may have shown differences if we had examined entorhinal cortex or hippocampus. Nevertheless, in view of the fact that changes in memory are an early marker of AD-DS, 90 any changes in the hippocampus of non-demented DS samples may prove to be largely developmental in origin. Another possibility to explain how a decrease in synapses may not be registered in changes in synaptic proteins would be an increase in the size of synapses; interestingly, in prior studies in the Ts65Dn mouse model we discovered an increase in apposition length in the motor cortex of excitatory synapse.…”

Section: Neuronal and Synaptic Changes During Development And With Ad-dsmentioning

confidence: 99%

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

Chen

Zuo

Becker

et al. 2022

Alzheimer's & Dementia

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Introduction: Synaptic failure, a hallmark of Alzheimer's disease (AD), is correlated with reduced levels of synaptic proteins. Though people with Down syndrome (DS) are at markedly increased risk for AD (AD-DS), few studies have addressed synapse dysfunction. Methods: Synaptic proteins were measured in the frontal cortex of DS, AD-DS, sporadic AD cases, and controls. The same proteins were examined in the Dp16 model of DS. Results: A common subset of synaptic proteins were reduced in AD and AD-DS, but not in DS or a case of partial trisomy 21 lacking triplication of APP gene. Pointing to compromised synaptic function, the reductions in AD and AD-DS were correlated with reduced SNARE complexes. In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD-DS; reductions were impacted by both age and increased App gene dose.

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Section: Neuronal and Synaptic Changes During Development And With Ad-dsmentioning

confidence: 99%

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

Chen

Zuo

Becker

et al. 2022

Alzheimer's & Dementia

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“…Current research is focused on development, cognition, with the goal of maximizing functional outcomes and improving their quality of life. Great strides have been made in observational and behavioral research in DS, with thorough characterization of development and cognition [1,2], as well as development of new tools to detect AD-related cognitive decline in adulthood [3,4]. Working groups have also evaluated potential outcome measures that can be used in clinical trials in the areas of cognition and behavior [5].…”

Section: Current State Of Clinical Trials In the Down Syndrome Popula...mentioning

confidence: 99%

Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group

Baumer

Becker

Capone

et al. 2022

J Neurodevelop Disord

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The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019.

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“…Andrew Aschenbrenner (USA) analyzed data from 5 longitudinal cohorts to identify specific cognitive domains that are most sensitive to rates of change in healthy adults with DS. A panel of experts was convened to agree on which particular measures to include in the final cognitive test battery [Aschenbrenner et al, 2021]. Criteria considered included ease of administration and scoring in a global clinical trial (i.e., the test must not be culturally specific).…”

Section: The H21/life-dsr Cognitive Test Battery: Identification Of A...mentioning

confidence: 99%

Innovating Therapies for Down Syndrome: An International Virtual Conference of the T21 Research Society

et al. 2022

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Research focused on Down syndrome continued to gain momentum in the last several years and is advancing our understanding of how trisomy 21 (T21) modifies molecular and cellular processes. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. During the COVID pandemic, T21RS held its first virtual conference program, sponsored by the University of California at Irvine, on June 8–10, 2021 and brought together 342 scientists, families, and industry representatives from over 25 countries to share the latest discoveries on underlying cellular and molecular mechanisms of T21, cognitive and behavioral changes, and comorbidities associated with Down syndrome, including Alzheimer’s disease and Regression Disorder. Presentations of 91 cutting-edge abstracts reflecting neuroscience, neurology, model systems, psychology, biomarkers, and molecular and pharmacological therapeutic approaches demonstrate the compelling interest and continuing advancement toward innovating biomarkers and therapies aimed at ameliorating health conditions associated with T21.

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Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease

Abstract: Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting predementia stages.

Cited by 14 publications

References 35 publications

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group

Innovating Therapies for Down Syndrome: An International Virtual Conference of the T21 Research Society

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