%0 Journal Article %J J Alzheimers Dis %D 2021 %T Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome. %A Petersen, Melissa E %A Rafii, Michael S %A Zhang, Fan %A Hall, James %A Julovich, David %A Ances, Beau M %A Schupf, Nicole %A Krinsky-McHale, Sharon J %A Mapstone, Mark %A Silverman, Wayne %A Lott, Ira %A Klunk, William %A Head, Elizabeth %A Christian, Brad %A Foroud, Tatiana %A Lai, Florence %A Diana Rosas, H %A Zaman, Shahid %A Wang, Mei-Cheng %A Tycko, Benjamin %A Lee, Joseph %A Handen, Benjamin %A Hartley, Sigan %A Fortea, Juan %A O'Bryant, Sid %X

BACKGROUND: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.

OBJECTIVE: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.

METHODS: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.

RESULTS: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.

CONCLUSION: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.

%B J Alzheimers Dis %V 79 %P 671-681 %8 2021 Jan 19 %G eng %N 2 %& 671 %R 10.3233/JAD-201167 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Cerebrovascular Disease and Neurodegeneration in Alzheimer's Disease with and without a Strong Family History: A Pilot Magnetic Resonance Imaging Study in Dominican Republic. %A Piriz, Angel %A Reyes, Dolly %A Narkhede, Atul %A Guzman, Vanessa A %A Viqar, Fawad %A Meier, Irene B %A Budge, Mariana %A Mena, Pedro %A Dashnaw, Stephen %A Lee, Joseph %A Reitz, Christiane %A Gutierrez, Jose %A Campos, Luis %A Medrano, Martin %A Lantigua, Rafael %A Mayeux, Richard %A Brickman, Adam M %X

The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status.

%B J Alzheimers Dis %V 66 %P 1519-1528 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/30412503?dopt=Abstract %R 10.3233/JAD-180807