Blood-based AD biomarkers profile in CAPCOG-TBI study

Ut Southwestern Medical Center, Dallas TX

Investigators

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Abstract

Sustaining a traumatic brain injury (TBI) can lead to an onset of and/or accelerate Alzheimer’s Disease (AD)-related neurodegeneration process.1Therefore, TBI is considered as a risk factor for AD and AD-related dementias (ADRD).2-5 Understanding of the pathophysiological mechanisms by which TBI contributes to ADRD onset and progression is a prominent research priority for the NIH.2 Recent development of blood-based AD biomarkers such as Aβ42/Aβ40 and phosphorylated tau (p-tau, e.g., p-tau 217) has shown its potential value for preclinical AD diagnosis6 and has been used in longitudinal observational studies and in clinical trials to assess changers in AD pathology.7 Mounting evidence also shows the importance to include nonspecific blood-based neuro-injury and inflammation biomarkers such as glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in ADRD research to identify co-existing pathology which may also contribute to cognitive symptoms.6 To date, it is unclear whether the presence of AD biomarkers after TBI indicates an independent AD-related pathology or a TBI-related pathology. Our ongoing ADRD-related project (R01NS129934), “Cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury (CAPCOG-TBI)”, is a longitudinal, observational study to understand the role of cerebrovascular dysfunction in cognitive and neuroimaging outcomes in persons with TBI. In CAPCOG-TBI, we will enroll 100 patients with TBI and 30 orthopedic trauma controls (OTC) during the first week after the indexed injury and follow them for one year. Besides cerebrovascular function measures, detailed pre-existing medical history and TBI injury and treatment history are collected during the acute stage. Cerebrovascular function along with blood sample collection, neurocognitive assessment, global functional outcome, and multimodality brain MRI are obtained at 3M and 12M postinjury. Blood samples are banked at BioSEND where APOE genotype will be performed as a part of the quality control process. Thus, this study provides a unique opportunity to reveal TBI-related longitudinal changes in blood-based AD biomarkers and their relationship with changes in cerebrovascular function, neuroimaging, and cognitive outcomes. The primary goal of this administrative supplement proposal is to measure changes in blood-based AD biomarkers after TBI and their associations with cerebrovascular injury, cognitive outcome, and neurodegeneration. To achieve this goal, we will quantify changes in blood-based AD biomarkers (Aβ42/Aβ40, total tau, p-tau 217, %p-tau217), GFAP, and NfL at three time points (<1 week, 3M, and 12M) after TBI in CAPCOG-TBI participants to address the following aims: 1) To quantify the temporal profile of changes in blood-based AD biomarkers after TBI. 2) To examine the temporal association of changes in blood-based AD biomarkers with cerebrovascular function after TBI. 3) To examine the associations of changes in blood-based AD biomarkers and cerebrovascular function with brain neurodegeneration and cognitive outcome after TBI.