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: 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.

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: 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.

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: 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 (APOEε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the APOEε4 genotype is associated with microglial reactivity in the living human brain.

Biomarkers.

Background: Recent anti-amyloid clinical trials have incorporated plasma glial fibrillary acidic protein (GFAP) as an exploratory endpoint, reporting a notable decrease in plasma GFAP levels over time. Additionally, plasma GFAP has been associated with Aβ pathology and cognitive decline in individuals with cognitive impairment, making it a robust biomarker of neuroinflammation for Alzheimer's disease (AD). Here, we tested the utility of changes in plasma GFAP as a secondary endpoint in AD clinical trials focusing on cognitively impaired (CI) individuals.

Biomarkers.

Background: It has been proposed that microglia release of proinflammatory factors reactive to amyloid plaques constitutes an early event leading to tau pathology. Here, we assessed how the rate of progression of tau-PET and the rate of change in plasma pTau217 are affected by baseline levels of amyloid-β and neuroinflammation.

Methods: We included 93 individuals from TRIAD cohort: 11 young individuals, 57 cognitively unimpaired elderlies, 15 with mild cognitive impairment and 10 individuals with Alzheimer's Disease.

Biomarkers.

Background: Biomarkers promise to significantly improve the differential diagnosis of Alzheimer's disease (AD). Plasma biomarkers, such as phosphorylated tau (p-tau), have shown potential in diagnosing AD with high accuracy. Unlike the widely-used [18 F]FDG-PET diagnostic biomarker in clinical practice, plasma p-tau is specific to AD and can provide an affordable and scalable diagnostic tool.

Biomarkers.

Background: We showed that plasma GFAP (a proxy of astrocyte reactivity) abnormality is key to unleashing Aβ effects on tau phosphorylation in preclinical AD. This suggests that selecting cognitively unimpaired(CU) individuals with both high Aβ and plasma GFAP could offer an early time window in the disease, but with an increased risk of developing tau pathology. Here, we tested the utility of plasma GFAP for population enrichment in clinical trials focusing on CU individuals.

Biomarkers.

Background: Recent evidence indicated that cognitive impairment is more closely associated with the spatial extent of tauopathy (SEOT) than with tau load. It remains unclear whether this is also true for other markers of Alzheimer's disease (AD) severity, such as fluid levels of phosphorylated tau (pTau). Here, we compared the link between fluid pTau and the SEOT and tau load in the brain, as assessed by PET.

Biomarkers.

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.

Biomarkers.

Background: Tau aggregates in Alzheimer's disease (AD) induce loss of synapses and neurons, leading to cognitive impairment. Predicting tau and neurodegeneration temporal evolution could be used for prognostication and for assessing results of therapeutic trials. Tau PET and MRI volumetry are reliable markers of disease stage, but cost and radiation protection considerations limit research measurement frequency, lowering the accuracy of disease progression modeling.

Biomarkers.

Background: Aβ plaques are the first detectable signs of AD pathology. Our group recently demonstrated that the astrocyte activation marker, glial fibrillary acidic protein (GFAP), has a pivotal role in the association between Aβ burden and tau phosphorylation. However, the role of astrocyte activation in individuals that do not present detectable Aβ pathology using biomarkers is still underexplored.

Biomarkers.

Background: The potential clinical utility of plasma biomarkers for biological staging of AD demands definition and validation of cutoff values. Plasma ptau-217 and GFAP have accurately predicted core pathological changes such as tau aggregation and amyloid (Aβ) deposition, being proposed as complementary biomarkers. Thus, we aim to test a staging framework with plasma GFAP and ptau-217 using cuttof values to predict Aβ/Tau PET stages and compare its performance with an artificial intelligence (AI) prediction model.

Biomarkers.

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.

Biomarkers.

Background: Timely and non-invasive prediction of amyloid status are pivotal in Alzheimer's disease (AD) diagnostics. This research leverages T1 MRI images to predict amyloid positivity or negativity, offering an economical and less invasive alternative to amyloid PET scans. Using the comprehensive TRAID dataset from McGill University, the study evaluates a spectrum of cognitive conditions including AD, atypical AD, Cognitively Normal (CN), Mild Cognitive Impairment (MCI), MCI not due to AD, Suspected Non-Alzheimer's Pathophysiology (SNAP), and Vascular MCI (VMCI).

Developing Topics.

Background: The presence of cortical amyloid-beta pathology is associated with white matter microstructural changes in Alzheimer's disease (AD), especially in tracts associated with memory. However, the relationships between tract-specific neuroinflammation and plasma markers of astrogliosis is underexamined; similarly, the involvement of tau neurofibrillary tangles is unclear in neuroinflammation. Here, we investigated the association between plasma glial fibrillary acidic protein (GFAP) and changing proportion of intravoxel freewater-a microstructural change associated with neuroinflammation-within white matter tracts vulnerable to AD.

Developing Topics.

Background: Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease (AD). Antibody-based immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in AD research. A novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - was developed to improve the sensitivity of traditional proximity ligation assays and offer a comprehensive outlook for protein biomarkers in neurodegenerative diseases.

Alzheimer's Imaging Consortium.

Background: Recent evidence indicated that cognitive impairment is more closely associated with the spatial extent of tauopathy (SEOT) than with tau load. It remains unclear whether this is also true for other markers of Alzheimer's disease (AD) severity, such as fluid levels of phosphorylated tau (pTau). Here, we compared the link between fluid pTau and the SEOT and tau load in the brain, as assessed by PET.

Alzheimer's Imaging Consortium.

Background: Tau aggregates in Alzheimer's disease (AD) induce loss of synapses and neurons, leading to cognitive impairment. Predicting tau and neurodegeneration temporal evolution could be used for prognostication and for assessing results of therapeutic trials. Tau PET and MRI volumetry are reliable markers of disease stage, but cost and radiation protection considerations limit research measurement frequency, lowering the accuracy of disease progression modeling.

Alzheimer's Imaging Consortium.

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).

Alzheimer's Imaging Consortium.

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.

Alzheimer's Imaging Consortium.

Background: The potential clinical utility of plasma biomarkers for biological staging of AD demands definition and validation of cutoff values. Plasma ptau-217 and GFAP have accurately predicted core pathological changes such as tau aggregation and amyloid (Aß) deposition, being proposed as complementary biomarkers. Thus, we aim to test a staging framework with plasma GFAP and ptau-217 using cuttof values to predict Aß/Tau PET stages and compare its performance with an artificial intelligence (AI) prediction model.

Alzheimer's Imaging Consortium.

Background: It has been proposed that microglia release of proinflammatory factors reactive to amyloid plaques constitutes an early event leading to tau pathology. Here, we assessed how the rate of progression of tau-PET and the rate of change in plasma pTau217 are affected by baseline levels of amyloid-ß and neuroinflammation.

Methods: We included 93 individuals from TRIAD cohort: 11 young individuals, 57 cognitively unimpaired elderlies, 15 with mild cognitive impairment and 10 individuals with Alzheimer's Disease.