Longitudinal multicenter head-to-head harmonization of tau PET tracers
Principal Investigator: Tharick Pascoal
Funding agency: National Institute on Aging
Period: July 2021 – June 2026
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 affinities 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
Principal Investigator: Tharick Pascoal
Funding agency: National Institute on Aging
Period: March 2022 – February 2027
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 (AACSF)
Principal Investigator: Tharick Pascoal
Funding agency: Alzheimer’s Association
Period: July 2020 – June 2023
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 (AARF-D)
Principal Investigator: Bruna Bellaver
Funding agency: Alzheimer’s Association
Period: October 2022 – October 2026
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 (AARF-D)
Principal Investigator: Pamela Lukasewicz Ferreira
Funding agency: Alzheimer’s Association
Period: June 2022 – August 2026
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.
A deep learning tool to generalize Tau PET to predict AD progression
Principal Investigator: Guilherme Bauer Negrini
Funding agency: Alzheimer’s Association
Period: September 2023 – August 2026
This study aims to develop a user-friendly tool for predicting Alzheimer’s disease (AD) progression using 3D tau positron emission tomography (PET) images, irrespective of tau tracers. We have three primary objectives: train Deep Learning models on large-scale datasets of Flortaucipir and MK-6240 tau PET tracers to predict clinical progression; enhance model performance with transfer learning on head-to-head acquired tau PET scans; and generalize to other tau tracers. By leveraging datasets with longitudinal data, including Flortaucipir and MK-6240 tau PET imaging, clinical, cognitive, and complementary fluid biomarker data, we intend to build robust models for AD prediction.
Association between longitudinal changes in plasma GFAP and AD progression
Principal Investigator: Sarah Abbas
Funding agency: Alzheimer’s Association
Period: September 2023 – August 2026
Recently, there has been a great focus on how other processes contribute to the progression of Alzheimer’s disease (AD), one of which is a malfunctioning of a population of cells called astrocytes. Astrocytes are involved in various regulatory brain activities to help the brain function normally. In AD, astrocytes are commonly associated with inflammation and can shift into an abnormal ‘reactive state,’ a process known as astrocyte reactivity. These reactive cells play a key role in worsening the disease, leading to greater memory loss and other cognitive difficulties. Moreover, when astrocytes are abnormal, they increase the release of proteins that can be measured in patients’ blood. We aim to analyze the level of one of these proteins, known as ‘GFAP’ released by reactive astrocytes and investigate how this protein changes over time. This will help shed light on how it may be associated with the worsening of AD.