Biomarkers.

Background: The association between [F]Flortaucipir (FTP) and [F]MK6240, two commonly used tau-PET tracers in Alzheimer's disease (AD), varies due to distinct binding properties and off-target signal regions. Our study aims to elucidate the biological factors influencing this association and evaluate the applicability of a common equation across different on-target regions.

Method: 113 individuals from the HEAD dataset (11 young, 58 cognitively unimpaired elderly, and 44 cognitively impaired) underwent [F]MK6240, [F]FTP and Aβ-PET scans.

Biomarkers.

Background: The detection and monitoring of Alzheimer's disease (AD) biomarkers in plasma are crucial for early diagnosis and prognosis. However, the stability of plasma AD biomarkers can be compromised by the degradation caused by endogenous proteases present in blood. The efficacy of protease inhibitors in mitigating this degradation is yet to be established.

Biomarkers.

Background: Differences between on- and off-target retention characteristics between [F]MK6240 and [F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [F]MK6240 (MK) and [F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid-β (Aβ) PET scan ([C]PIB or [F]NAV4694) and two tau-PET scans: [F]MK (90-110 minutes post-injection) and [F]FTP (80-100 minutes post-injection).

Biomarkers.

Background: Specific PSEN1 mutations cause early-onset AD but their effects on blood biomarker levels are unknown. We evaluated autopsy-confirmed individuals affected by six different PSEN1 mutations; two of known (L381V, C410Y) and three (A426P/E318G, M233L, and V261I) of unknown pathogenic status. The sixth patient had Autosomal Dominant AD (ADAD) not yet genotyped.

Biomarkers.

Background: Trisomy 21 in Down syndrome (DS) is associated with an earlier accumulation of beta-amyloid (Aβ) plaques and a higher rate of Alzheimer's Disease due to the triplication of the amyloid precursor protein gene. In this study we compare accumulation rates of Aβ measured with [C-11]PiB PET between large longitudinal cohorts of DS and neurotypical (NT) participants at a single site.

Methods: Participants imaged at the University of Wisconsin with ≥2 PiB scans and ≥2 years between scans were included in this study.

Biomarkers.

Background: Given the increasing usage of plasma biomarkers for Alzheimer's disease (AD) studies, it is necessary to better understand relationships between plasma biomarker and PET and MR imaging outcomes, particularly within the AT(N) framework.

Method: We evaluated plasma samples from 233 subjects (age 74.05.

Biomarkers.

Background: Default mode network (DMN) resting state connectivity has been correlated with heightened amyloid and tau - hallmarks of Alzheimer's Disease (AD). Tau is postulated to impact a meta-temporal area including DMN-associated regions like amygdala, entorhinal cortex, fusiform gyrus, parahippocampus, inferior temporal, and middle temporal gyrus. We recruited individuals with varying cognitive status to undergo resting state connectivity and imaging with two tau tracers (Flortaucipir and MK6240).

Biomarkers.

Background: Tau-PET tracers have been used to diagnose and stage Alzheimer's disease. However, different tau tracers present distinct patterns of binding throughout the brain, challenging the harmonization of their results. We hypothesize that the choice of a reference region can impact the harmonization of the tau-PET standardized uptake value ratio (SUVR).

Biomarkers.

Background: Standardizing tau pathology quantification in vivo is challenged by differences in binding characteristics between tau-PET tracers. The HEAD study aims to generate a leading, longitudinal head-to-head dataset of MK-6240, Flortaucipir, RO948, and PI-2620 tau-PET to harmonize these tracers' outcomes and develop tools allowing for the generalization of findings across large studies and trials. Here, we present current advancements in building the HEAD study cohort and dataset.

Biomarkers.

Background: Harmonization of the two most commonly used Tau PET tracers, 18F-Flortaucipir and 18F-MK6240 has proven to be complex. Unlike the centiloid scale for amyloid tracers, Tau PET SUVRs of the two tracers are not linearly comparable and vary markedly in dynamic range and sensitivity.

Method: Tau PET SUVRs for Braak stage (1-6) in 18F-MK6240 and 18F-Flortaucipir were obtained from the Longitudinal multicenter head-to-head harmonization of tau-PET tracers (HEAD) project.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: The HEAD study aims to collect a large dataset of multiple tau-PET tracers to provide robust anchor values for tau-PET harmonization. Here, we tested the hypothesis that anchoring two tau tracer uptake values using head-to-head measurements has the potential to generate an accurate universal tau-PET scale, named Uniτ(tau).

Methods: We assessed 200 individuals across the aging and AD spectrum (Training: HEAD data freeze 2.

Biomarkers.

Background: Plasma biomarkers have been widely evaluated as surrogate markers for brain Alzheimer's disease (AD) pathology. However, studies in diverse populations with lower socioeconomic status (SES) are limited. We evaluated associations between different plasma biomarkers and brain amyloid beta (Aβ) and tau positron emission tomography (PET) in a longitudinal cohort of cognitively normal participants from a medically- and economically-underserved Rust Belt region of Western Pennsylvania, USA.

Biomarkers.

Background: Identifying individuals' levels of tau PET pathology could prove to be beneficial in clinical settings, given that emerging therapies aimed reducing Aβ seem to be most effective in these individuals. Here, we present the cases of four patients who visited the memory clinic at the University of Pittsburgh Medical Center between June and December 2023 and underwent both Aβ and tau-PET scans.

Method: These individuals had standard clinical and cognitive outcomes, typical blood tests order in patients with memory impairment, MRI, and, as part of the HEAD study, PET PIB Aβ and two tau PET tracers (MK6240 and Flortaucipir).

Biomarkers.

Background: Tau PET tracers are employed to measure the accumulation of tau in vivo in the brain. Each tau tracer possesses unique characteristics, including binding affinity, sensitivity, and specificity to tau aggregates. This study leverages the HEAD study dataset, which is currently performing baseline tau PET tracers and conducting multiple clinical and cognitive assessments.

Biomarkers.

Background: Utilizing PET amyloid-beta (Aβ) and tau for staging Alzheimer's Disease (AD) has demonstrated potential in identifying individuals with varying degrees of disease severity, applicable to both clinical trials and practice. However, the diverse binding characteristics of tau tracers pose challenges to the application of this staging across different ligands. In this study, we evaluate a novel staging framework proposed by the AA working group, employing Aβ PET and either [F]MK6240 or [F]Flortaucipir in individuals participating in a head-to-head study of tau PET tracers.

Biomarkers.

Background: Tau PET thresholds should detect early tau deposition and predict cognitive decline. We evaluated the relationships between the BETTH-derived sensitivity and specificity tau thresholds (Gogola et al, doi:10.2967/jnumed.

Biomarkers.

Background: Tau PET provides continuous measurements of tau tangle pathology in the human brain. However, establishing cutoffs is crucial for selecting individuals for treatment in clinical trials or practice. In the absence of postmortem data, PET cutoffs must be established using statistical methods based on what is considered normal tracer uptake.

Biomarkers.

Background: Gaussian smoothing to a common image resolution is frequently employed to harmonize Aβ PET in multisite studies. However, spatial smoothing of PET can increase spill-over contamination between neighboring regions. Geometric transfer matrix partial volume correction (PVC) has been applied, in turn, to correct for such contamination.

Biomarkers.

Background: The HEAD study focuses on collecting an extensive dataset from various tau-PET tracers, aiming to establish robust anchor values, which are essential for harmonizing tau-PET measurements. Here, we aim to showcase the capability of converting 3D tau-PET images into a common scale using the Universal Tau-PET Scale, Uniτ (tau), and to use these 3D images to subsequently obtain ROIs as needed.

Methods: We assessed 185 individuals across the aging and AD spectrum from the HEAD study, with [F]Flortaucipir and [F]MK-6240 tau-PET tracers.

Biomarkers.

Background: Imaging and plasma biomarkers are widely used in Alzheimer's disease (AD) observational studies and clinical trials. Due to the lack of racial or ethnic diversity in earlier studies, a more complete understanding of biomarker differences across racialized groups is needed. Further, results from the few previous studies have disagreed on both the magnitude and direction of AD biomarker differences in racialized groups.

Biomarkers.

Background: Blood-based biomarkers able to detect atypical neuropathology could serve as a cost-effective and noninvasive screening to include participants with Down syndrome (DS) in anti-amyloid clinical trials. Accurately placing these novel biomarkers on the AD pathological cascade as proposed by the AT(N) framework informs relative disease progression of individuals. This work examines associations between plasma pTau217 accumulation, PET amyloid positivity, and cognitive status in adults with Down syndrome.

Biomarkers.

Background: Plasma p-tau217 is probably the best-performing blood biomarker to detect brain amyloid-beta (Aβ) accumulation. However, previous studies were mostly performed in highly selected cohorts. Thus, it is unclear if it can be used independently of confirmatory neuroimaging tests to identify individuals with abnormal brain Ab load in the wider population where positron emission tomography (PET) may be unavailable.

Biomarkers.

Background: Amyloid β (Aβ) deposition in the brain is a pathological hallmark of Alzheimer's disease (AD). While immunoprecipitation-mass spectrometry (IP-MS) stands out as an accurate method for quantifying blood-based Aβ peptides, its major limitations such as prolonged sample preparation, extensive analysis time, large specimen volume, and high costs, present opportunities for improvement. Consequently, we aimed to develop a novel plasma IP-MS Aβ assay that employs simplified and significantly shorter analytical procedures, along with much-reduced sample volumes.

Biomarkers.

Background: Alzheimer's disease (AD) is a multifaceted condition associated with various brain pathologies, necessitating diverse biomarkers for precise prognosis, diagnosis, clinical management, and therapeutic development/evaluation. The integration of multiple biomarkers into a single test can enhance efficiency, reduce analytical errors, and save on specimen volume. Alamar Biosciences recently introduced the NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ∼120 analytes.