The prevalence of tau‐PET positivity in aging and dementia.

Background: Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e.

Exploring a weighted composite score for harmonization of 18F‐MK6240 and 18F‐ Flortaucipir: linearity and correlations with cognitive measures in a head‐to‐head tau PET dataset – The HEAD Study.

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.

The Berkeley PET Imaging Pipeline: Harmonization of Alzheimer’s disease PET biomarkers across studies.

Background: Collection of neuroimaging data is resource‐intensive. Multi‐site studies have emerged as an effective way to amass large collections of PET scans, but data collected across many sites and scanners require specialized processing approaches. The Berkeley PET Imaging Pipeline (BPIP) and tools for numerical data post‐processing allow us to 1) process multi‐site and multi‐study PET scans using harmonized, largely automated tools and 2) disseminate numerical quantitative data.

The prevalence of tau‐PET positivity in aging and dementia.

Background: Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e.

Quantification of tau pathology in the basal forebrain: Associations with age, amyloid, brain structure and cognition.

Background: Tau pathology accumulates early in the basal forebrain (BF) in Alzheimer’s disease (AD). The feasibility of measuring in vivo BF tau is unclear given PET resolution and possible partial volume effects of off‐target signal (OTS) which varies by tracer.

Method: We compared measurements of tau in cognitively unimpaired older adults with either an FTP or MK6240 scan: 93 FTP scans from the Berkeley Aging Cohort Study (BACS), 424 FTP scans from ADNI (N = 517 FTP scans; 72.

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.

Quantification of tau pathology in the basal forebrain: Associations with age, amyloid, brain structure and cognition.

Background: Tau pathology accumulates early in the basal forebrain (BF) in Alzheimer’s disease (AD). The feasibility of measuring in vivo BF tau is unclear given PET resolution and possible partial volume effects of off‐target signal (OTS) which varies by tracer.

Method: We compared measurements of tau in cognitively unimpaired older adults with either an FTP or MK6240 scan: 93 FTP scans from the Berkeley Aging Cohort Study (BACS), 424 FTP scans from ADNI (N=517 FTP scans; 72.

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).

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).

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.

Generalizability of demographic and genetic variable interactions with amyloid driving tau burden in a heterogeneous group of cognitively normal older adults: A multi‐cohort study.

Background: Efforts to increase heterogeneity in cohorts of cognitively normal older adults with Alzheimer’s disease (AD) neuroimaging biomarkers have resulted in large datasets with differing characteristics. It is unclear whether associations between AD biomarkers and key demographic and genetic factors are generalizable across heterogeneous cohorts.

Method: PET and MR scans from cognitively normal older adults aged >55 in the Berkeley Aging Cohort Study (BACS), ADNI, the Health and Aging Brain Study‐Health Disparities (HABS‐HD) and POINTER Imaging were processed using harmonized pipelines.

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.

Impact of anchoring cutoff point of tau positivity on CU young or older adults using Flortaucipir and MK‐6240 – Head Study.

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.

Creating Universal Tau PET Scale (Uniτ) Parametric Images – The HEAD Study.

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.

Association between medial temporal and neocortical Tau SUVR across tau imaging agents: HEAD Study.

Background: The association between medial temporal and neocortical SUVR depends on availability of cortical tau. However, tracer differences in affinity and off‐target binding might interfere in these associations. Here, we examined the association between medial temporal and neocortical SUVR using voxel‐based approach.

Patterns of Association of Tau Across Cortical Regions Differ Between [F]MK6240 and [F]Flortaucipir.

Background: This study aims to investigate the differential patterns of association in tau protein imaging across cortical regions using two distinct Tau imaging agents: [18F]MK6240 and [18F]Flortaucipir. The underlying hypothesis posits that variations in the properties of these tracers, such as affinity and off‐target effects, influence the observed patterns of association in neuroimaging.

Method: To test this hypothesis, a comprehensive study was conducted involving 104 subjects part of the HEAD study at McGill University: 53 cognitively normal (CN), 19 with mild cognitive impairment (MCI), 9 with Alzheimer's Disease (AD) and 23 non‐AD.

CU PET Aβ and Tau Positive Individuals Show Impairment in MoCA Delayed Recall.

Background: Identification of cognitively unimpaired (CU) individuals who may progress to mild cognitive impairment (MCI), is a pressing issue in the Alzheimer’s disease (AD) field, since therapeutic interventions may be more effective in the absence of cognitive impairment and neurodegeneration. CU individuals positive for amyloid and tau PET are very likely in the AD pathway. In out‐patient cognitive screening, we use rapid and simple tests such as The Montreal Cognitive Assessment (MoCA) ‐ a composite of executive, visuospatial, naming, attention, language, abstraction, delayed recall, and orientation performances.

Voxel‐wise comparison of [F]MK6240 and [F]Flortaucipir for the diagnosis of individuals across the Alzheimer’s disease spectrum – the HEAD study.

Background: In vivo studies using the tau PET tracers have shown high performance for the diagnosis of Alzheimer’s disease dementia and patterns of tracer uptake that resemble those observed in post‐mortem studies. However, tau tracers present distinct patterns of binding that might influence their performance in detecting AD pathology. In a head‐to‐head study, we investigated the performance of [F]MK6240 and [F]Flortaucipir for the diagnosis of AD.

4, blood glucose levels, peripheral inflammation, and cognitive change among postmenopausal women in the Women’s Health Initiative.

Background: Older women have a higher prevalence of Alzheimer’s disease relative to comparably aged men. Although the biological mechanisms driving this sex difference remain elusive, emerging data suggest that longevity, 4, inflammation, and blood glucose levels may play roles. Our objective was to examine the associations of 4, high sensitivity‐C‐reactive protein (hs‐CRP), and fasting blood glucose levels with cognitive changes over time among women enrolled in two ancillary studies of the Women’s Health Initiative (WHI).

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

Background: Differences between on‐ and off‐target retention characteristics between [18F]MK6240 and [18F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [18F]MK6240 (MK) and [18F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid‐β (Aβ) PET scan ([11C]PIB or [18F]NAV4694) and two tau‐PET scans: [18F]MK (90‐110 minutes post‐injection) and [18F]FTP (80‐100 minutes post‐injection).

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.