Longitudinal multicenter head-to-head harmonization of tau PET tracers

Tau PET imaging is an important tool to study aging and Alzheimer’s disease in research and to test the impact of therapeutics in clinical trials. However, different tau PET tracers have different affinity for tau aggregates and off-target signal profiles, making it difficult to compare results across studies using distinct tau tracers. In this study, we will compare cross-sectional and longitudinal tau measures obtained with the two most widely used tau PET tracers, [18F]Flortaucipir and [18F]MK6240, head-to-head in the same volunteers to elucidate the advantages and caveats of their use in research cohorts, clinical trials, and clinical practice.

Head-to-head comparisons of high-performance plasma phospho-tau epitopes for the detection of Alzheimer’s disease

Three plasma phosphorylated tau epitopes (p-tau231, p-tau181, p-tau217) have recently emerged as important tools to study Alzheimer’s disease (AD) pathophysiology. However, the difference in performance between these epitopes to identify the AD continuum is poorly understood, making it difficult for the field to choose the plasma p-tau epitope or combination of epitopes that will advance for widespread use in clinical trials and practice. We will measure the p-tau231, p-tau181, p-tau217 assays in longitudinally collected plasma samples, with associated positron emission tomography tau and amyloid-beta, from individuals across the AD spectrum to elucidate the performance of each p-tau epitope to use in research and clinical settings.

High-performance plasma phosphor-tau predicts dementia, tau and amyloid PET

In this project, we will test whether a newly developed blood test can provide the first rapid, cost-effective, and scalable diagnostic test for Alzheimer’s disease (AD). Currently, the diagnosis of AD is based primarily on the clinical examination of the patient, which is only about 70% accurate. Thus, assessing the presence of AD pathology in patients using a simple blood test can completely change the landscape of AD research and patient care, allowing accurate and cost-effective diagnosis of AD. The preliminary results presented here suggest an unprecedented advance for diagnosing AD with more than 90% accuracy using a blood test, bypassing the need for any complementary testing. The present research proposal seeks to extend these preliminary results in a large human population of AD patients and controls, aiming to validate this new blood test for use in clinical practice.

Glial signatures of tau propagation in Alzheimer’s disease

The trigger for tau propagation is commonly attributed to amyloid-β (Aβ). However, the low concentration of Aβ in the mesial temporal regions and the existence of individuals tau-positive but Aβ-negative suggests Aβ-independent tau spreading pathways. The neurocentric focus of dementia research has delayed understanding the complex roles of other cell types in AD pathology, such as the glial cells. We hypothesize that glial cells are directly involved in Aβ-independent tau spreading and that measuring proteins released from these cells would allow identifying tau spreading patterns throughout the brain. The goal of this study is to identify glial cell signatures associated with amyloid-β (A)-dependent and A-independent tau propagation in AD.

Racial and ethnic effects on plasma p-tau epitopes across AD spectrum

Blood-based methods measuring phosphorylated tau epitopes (p-tau) are currently the most promising blood-based biomarkers for Alzheimer’s disease (AD)-related tau pathology. However, several lines of evidence suggest that the measures obtained with different plasma p-tau epitopes may not be equivalent and may vary greatly depending on the disease stage. In addition, the generalizability of findings investigating plasma p-tau biomarkers may be limited since the analyzes were performed almost exclusively in Caucasian cohorts. Therefore, there is an urgent need to better characterize the p-tau biomarkers in people from different races and ethnic groups. This project aims to test the effects of race and ethnic groups in the cross-sectional and longitudinal concentrations of these plasma p-tau epitopes in different cohorts.