A Study on the Utility of Blood-Based Biomarkers for Alzheimer’s Disease in Predicting Cerebral Amyloid among Individuals with Down Syndrome

dc.creatorAwasthi, Shubhangien_US
dc.creatorZhang, Fanen_US
dc.creatorHall, Jamesen_US
dc.creatorMapstone, Marken_US
dc.creatorO'Bryant, Siden_US
dc.creatorPetersen, Melissaen_US
dc.descriptionResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, 2024 Student Research Award - 1st Placeen_US
dc.description.abstractPurpose: Down Syndrome (DS) is one of the most common genetic disorders. Individuals with DS show Alzheimer’s Disease (AD)-related neuropathology at a younger age, placing them at an increased risk for developing dementia. Limited research has explored the relationship between blood-based biomarkers and cerebral amyloid positivity. Our study examines the association between blood-based biomarkers and the presence of cerebral amyloid detected by PET scans in participants with DS. Methods: Data were analyzed on a cohort of n=368 participants with DS aged 30 and above. Proteomic assays of amyloid beta 40 (Aꞵ40) and 42 (Aꞵ42), total tau, neurofilament light (NfL), and phosphorylated tau181 (pTau181) were performed on plasma samples using Single Molecule Array (Simoa). Cerebral amyloid levels were obtained through PET Amyloid imaging. Covariates included age, gender, and presence of at least one APOε4 allele. Correlations were run using R statistical software. Random Forest analyses were conducted to examine the link between the select biomarkers and cerebral amyloid SUVR levels. Logistic regressions were also used in examining the utility of AD biomarkers in detecting cerebral amyloid positivity. Significance was set at p<0.05. Results: The biomarkers that significantly correlated with cerebral amyloid SUVR levels were Aꞵ42 (p=0.020), total tau (p<0.001), NfL (p<0.001), and pTau181 (p<0.001). There was no significant correlation between Aꞵ40 (p=0.888) and levels of cerebral amyloid. Regression analysis demonstrated a high correlation (R2 = 0.956) between the biomarkers and cerebral amyloid positivity. Our profile was accurate in detecting the presence of cerebral amyloid, yielding an area under the curve (AUC) of 0.9984, a positive predictive value (PPV/Precision) of 0.9571, sensitivity of 0.9853, and specificity of 0.9404. Conclusion: Our findings demonstrate that our proteomic profile consisting of the biomarkers Aꞵ40, Aꞵ42, total tau, NfL, and pTau181, and select demographics was highly accurate in predicting the presence of cerebral amyloid in our cohort. Having a less invasive and less costly screening tool, such as a blood-based biomarker profile, will allow for earlier detection of dementia in individuals who are at risk. Future research should explore these findings in the context of a larger cohort for increased generalizability.en_US
dc.description.sponsorshipNIH/NIA U19AG068054en_US
dc.titleA Study on the Utility of Blood-Based Biomarkers for Alzheimer’s Disease in Predicting Cerebral Amyloid among Individuals with Down Syndromeen_US