Biological Factors Influencing [18F]MK6240 and [18F]FTP Correlation in Target Regions.

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.

Comparison of tau‐PET tracers for in vivo Braak staging: the HEAD Study.

Background: Tau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.

Improving the preanalytical stability of Alzheimer’s disease plasma biomarkers: the impact of blood collection tubes supplemented with protease inhibitors.

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.

CSF and Plasma Proteomics in the AT groups. What is beyond amyloid and p‐tau?

Background: The research on Alzheimer’s disease (AD) has substantially advanced in relation to plasma biomarkers, such as pTau217, for the detection of amyloid (Aβ) pathology which identify, with high accuracy, individuals in the AD biological continuum. However, as these biomarkers become abnormal very early in the disease, biomarkers identifying more advanced disease stages and proxying pathophysiological processes beyond amyloidosis are still needed. Therefore, we have conducted a proteomic study, on plasma and CSF, aiming at identifying proteins reflecting pathological changes in AD.

Comparison of [F]MK6240 and [F]Flortaucipir standardized uptake values (SUVs): the HEAD study.

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).

Blood biomarker profiles in autopsy‐diagnosed carriers of different PSEN1 mutations relative to sporadic Alzheimer’s disease and controls.

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.

Inflammation links in Alzheimer’s Disease: connecting fluid proteomics and TSPO PET.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer’s disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid‐ β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Brain metabolic subtypes in Long Covid individuals from a Brazilian cohort.

Background: The Coronavirus disease 2019 (COVID‐19), caused by SARS‐CoV‐2, is one of the biggest health concerns of the century. Long COVID is one of the major sequelae from the infection and include persistent neurological manifestations. Brain images study suggest that Long COVID patients present distinct brain metabolic alterations.

Autoradiographic comparison of [11C]PiB and [18F]NAV4694 in post‐mortem human brain tissue.

Background: To evaluate the in vitro binding properties of [C]PiB and [F]NAV4694 head‐to‐head in post‐mortem human brain tissue.

Method: Autoradiography was used to assess uptake of [C]PiB and [F]NAV4694 in control (CN) and Alzheimer’s disease (AD) autopsy‐confirmed brain tissues. The study focuses on the analysis of the prefrontal cortex, inferior parietal cortex, posterior cingulate cortex and hippocampus sections in 11 CN and 11 AD cases.

Assessing the correlations between imaging and plasma biomarkers within the AT(N) framework.

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.

Association between Default Mode Network Connectivity Compared Between Two Tau Tracers (Flortaucipir vs. MK6240) – HEAD Study.

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).

Exploring the effects of using multiple different cerebellar reference regions to improve tau‐PET harmonization ‐ The HEAD Study.

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).

Characterization of plasma biomarkers of individuals with amyloid‐independent increased tau positron‐emission tomography uptake.

Background: Increased uptake on Tau positron‐emission tomography (PET) is sometimes observed in the absence of amyloid β accumulation. This A‐T+ PET profile might represent primary age‐related tauopathy (PART), an amyloid β‐independent 3R/4R tauopathy observed in aging brains. Although A‐T+ individuals have been shown to follow a different cognitive trajectory compared to A‐T‐ and A+T+ individuals, it remains unknown how they differ in terms of plasma biomarkers.

Brain Glucose Metabolism Changes in Long‐COVID: A Brazilian Cohort Study.

Background: The COVID‐19 pandemic is a public health crisis, and its lasting consequences are not yet fully understood. Epidemiological data suggest that low‐ and middle‐income countries, such as Brazil, will bear a considerable burden of COVID‐19‐related comorbidities. Individuals who have survived COVID‐19 often report persistent symptoms, including neurological manifestations such as brain fog.

Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers: an overview of the HEAD study cohort.

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.

A polymorphism in RELN protects against amyloid‐driven tau pathology and cognitive decline in sporadic Alzheimer's disease.

Background: A rare reelin gene variant (RELN‐COLBOS mutation) delayed dementia onset in almost 30 years in an autosomal dominant Alzheimer’s disease (ADAD) carrier. This patient presented with high amyloid‐β (Aβ) plaque load, but low tau accumulation, suggesting that this single‐nucleotide polymorphism (SNP) in RELN conferred a resilience not only to cognitive decline but also to tauopathy in ADAD. However, whether RELN SNPs are also protective in sporadic Alzheimer’s disease (AD) is yet to be determined.

Universal tau PET scale (Uniτ) – The HEAD Study.

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.

Synergic effect of tau tangles and cortical thinning on cognitive decline in aging and Alzheimer’s disease.

Background: Tau burden has been found to be involved in brain atrophy during aging, especially in regions such as the parahippocampal gyrus. However, how tau levels at baseline are associated with trajectories of tau accumulation, cortical thinning and cognitive impairment remains poorly understood. The goal of this study was to assess tau rate of change in patients between baseline Tau+ and Tau‐ patients.

APOEε4 drives microglial activation in the medial temporal cortex in individuals across the AD spectrum.

Background: Microglial activation is an early phenomenon in Alzheimer’s disease (AD) that may occur prior to and independently of amyloid‐β (Aβ) aggregation. Compelling experimental evidence suggests that the apolipoprotein E ε4 (ε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the ε4 genotype is associated with microglial reactivity in the living human brain.

Late‐life hypertension acts together with amyloid‐β pathology to promote memory loss.

Background: Midlife hypertension (HTN) is a known risk factor for Alzheimer's disease (AD). However, it remains to be elucidated whether the effect of late‐life HTN is also present. Here, we aimed to assess the associations of late‐life HTN and amyloid‐β pathology (Aβ) with longitudinal changes in global cognition and different domains in cognitively unimpaired (CU) individuals.

Associations between plasma biomarkers and brain amyloid and tau pathologies in a population‐based cohort without evidence of cognitive impairment.

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.

Utility of plasma p‐tau217 as a secondary outcome for clinical trials across AD continuum.

Background: Blood‐based biomarkers offer a cost‐effective and simple alternative for clinical use in the context of Alzheimer's disease (AD). It has already been shown that plasma phosphorylated tau at threonine 217 (p‐tau217) is associated with amyloid (Aβ), neurofibrillary tau tangles, and cognitive decline. Longitudinal studies confirmed its ability to track AD progression.

Clinical use of tau PET in Aβ PET positive individuals: a case series.

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).

Direct comparisons of the associations between the tau PET tracers [F]Flortaucipir and [F]MK6240 with tests of general cognitive performance ‐ The HEAD study.

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.

Alzheimer's disease staging with [F]MK6240 and [F]Flortaucipir ‐ the HEAD study.

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.