Pedro Rosa

• MD PhD
• Professor (Associate) at McGIll UNiversity, Douglas Mental Health University Institute

Background: According to the World Health Organization (WHO), approximately 5% of children and 2.5% of adults suffer from attention deficit hyperactivity disorder (ADHD). This disorder can have significant negative consequences on people’s lives, particularly children. In recent years, methods based on artificial intelligence and neuroimaging techn...

INTRODUCTION Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)‐related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials. METHODS We estimated longitudinal progression,...

Background While the temporal profile of amyloid (Aβ) and tau cerebrospinal fluid (CSF) biomarkers along the Alzheimer’s disease (AD) continuum is well-studied, chronological changes of CSF proteins reflecting other disease-relevant processes, denoted ‘X’ in the ATX(N) framework, remain poorly understood. Methods Using an untargeted mass spectrome...

INTRODUCTION To understand the role of neuroinflammation in Alzheimer's disease (AD), we characterized immune‐related proteins in central and peripheral biofluids. METHODS Selection of participants from the Translational Biomarker of Aging and Dementia (TRIAD) cohort with available translocator protein (TSPO) positron emission tomography (PET), ce...

Background Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates. Methods To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions. Results Longitudinal and cross-sectional MCA in large agin...

Background: Amyloid plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer's disease; however, the potential for delaying the onset of clinical symptoms in asymptomatic people is unknown. The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) is an ongoing platform trial assessing the safety a...

Background Amyloid-β imaging through positron emission tomography (PET) has significantly transformed Alzheimer’s disease (AD) research. [¹¹C]PiB has been widely used for imaging β-amyloid plaques due to its high affinity and selectivity for amyloid deposits. [¹⁸F]AZD4694 is a more recently developed amyloid-PET imaging agent, which structurally re...

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma...

Alzheimer's disease (AD) dementia is characterized by significant molecular and phenotypic heterogeneity, which confounds its mechanistic understanding, diagnosis, and effective treatment. In this study, we harness the most comprehensive dataset of paired ante-mortem blood omics, clinical, psychological, and post-mortem brain multi-omics data and n...

Intracellular alpha-synuclein aggregates, known as Lewy bodies (LB), are commonly observed in Alzheimer’s disease (AD) dementia. Post-mortem studies have shown a higher frequency of neuropsychiatric symptoms among individuals with AD and LB co-pathology. However, the effects of in vivo-measured LB pathology on neuropsychiatric symptoms in AD remain...

Recently, conceptual systems for the in vivo staging of Alzheimer’s disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (bioma...

Purpose This study aimed to select robust features against lung motion in a phantom study and use them as input to feature selection algorithms and machine learning classifiers in a clinical study to predict the lymphovascular invasion (LVI) of non-small cell lung cancer (NSCLC). The results of robust features were also compared with conventional t...

Tau is a microtubule protein that is known to be hyperphosphorylated and to aggregate in several chronic neurodegenerative disorders. In many cases, in particular in Alzheimer’s disease, the degree of tau pathology has been demonstrated to correlate with cognitive deficits and/or decline. In Huntington’s disease (HD), a dominantly inherited neurode...

Alzheimer’s disease (AD) is associated with presymptomatic changes in brain morphometry and accumulation of abnormal tau and amyloid-beta pathology. Studying the development of brain changes prior to symptoms onset may lead to early diagnostic biomarkers and a better understanding of AD pathophysiology. AD pathology is thought to arise from a combi...

INTRODUCTION We assessed the prognostic accuracy of plasma p‐tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow‐up of 5.65 years after plasma collection (range 1.01–10.47). METHODS We included 215 participants from the PREVENT−AD cohort with plasma Aβ42/40 and p‐tau...

INTRODUCTION Epidemiological studies indicate a link between attention‐deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear. METHODS We computed weighted ADHD polygenic risk scores (ADHD‐PRS) in...

Background Blood-based biomarkers (BBMs) have emerged as promising tools to enhance Alzheimer’s disease (AD) diagnosis. Despite two-thirds of dementia cases occurring in the Global South, research on BBMs has predominantly focused on populations from the Global North. This geographical disparity hinders our understanding of BBM performance in diver...

Background Impaired kidney function has a potential confounding effect on blood biomarker levels, including biomarkers for Alzheimer’s disease (AD). Given the imminent use of certain blood biomarkers in the routine diagnostic work-up of patients with suspected AD, knowledge on the potential impact of comorbidities on the utility of blood biomarkers...

Introduction In vitro data from primates provide conflicting evidence about the suitability of the cerebellum as a reference region for quantifying type 5 metabotropic glutamate receptor (mGluR5) binding parameters with positron emission tomography (PET). Methods We first measured mGluR5 density in postmortem human cerebellum using [3H]ABP688 auto...

Importance Understanding the characteristics of discordance between plasma biomarkers and positron emission tomography (PET) results in Alzheimer disease (AD) is crucial for accurate interpretation of the findings. Objective To compare (1) medical comorbidities affecting plasma biomarker concentrations, (2) imaging and clinical features, and (3) c...

Patients with Alzheimer’s disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and...

According to the World Health Organization (WHO), approximately 5% of children and 2.5% of adults suffer from attention deficit hyperactivity disorder (ADHD). This disorder can have significant negative consequences on people’s lives, particularly children. In recent years, methods based on artificial intelligence and neuroimaging techniques, such...

Prevention of dementia due to Alzheimer’s disease (d/AD) requires interventions that slow the disease process prior to symptom onset. To develop such interventions, one needs metrics that assess pre-symptomatic disease progression. Familiar measures of progression include cerebrospinal fluid (CSF) biochemical and imaging analyses, as well as cognit...

We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Mo...

Background: Latin American countries present major health-related inequities due to historical, cultural, and social aspects. Recent evidence highlights that factors related to social and health disparities outweigh classic demographic factors in determining healthy brain aging in these populations. However, these analyses have not been conducted...

Lecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Wo...

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer’s disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau...

Background Screen failure due to amyloid negativity is yet a problem in clinical trials for anti‐amyloid drugs. In this context, clinical characteristics of patients presenting with cognitive decline may decrease the screen failure ratio by increasing the odds of selecting individuals with brain amyloid pathology. Herein, we aimed at estimating amy...

Background Anti‐amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid‐ and tau‐positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine‐learning prediction model to identify tau positivity in amyloid‐positive individuals using clinical...

Background Universities can play a very important role in providing post‐diagnosis dementia education and support to the community. The McGill University Dementia Education Program was founded in 2017 by Claire Webster, a former care partner and dementia care consultant with this aim. Mrs. Webster had no affiliation with the university prior to beg...

Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [18F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of t...

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 pTa...

Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...

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. Method We assessed 51 cog...

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 gener...

Background Higher educational attainment is frequently associated with lower risk of cognitive decline. Many neuroprotective factors have been suggested as the biological underpinnings of cognitive reserve (CR), though the neural basis of CR is yet unclear. Herein, we aim at investigating the effect of CR using educational attainment in individuals...

Background Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aß pathology and mediates tau‐p...

Background The association between [18F]Flortaucipir (FTP) and [18F]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...

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 c...

Background Alzheimer’s disease (AD) is classically viewed as a predominantly amnestic syndrome, with other cognitive and neuropsychiatric symptoms (NPS) being non‐integral associations. Emerging Evidence suggests that within typical AD, these symptoms are core features from the onset. Methods We employed K‐modes clustering on 2483 cognitively impa...

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...

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...

Background Recent studies showed that neuroinflammation plays a key role in triggering specific neuropsychiatric symptoms (NPS), such as irritability and agitation, in individuals with Alzheimer’s disease (AD). While prior studies showed an association between tau pathology and all NPS domains, the extent to which tau influences each specific NPS d...

Background Recent studies have suggested a transient glucose hypermetabolism in early phases of Alzheimer's Disease (AD), which is followed by a characteristic glucose hypometabolism in dementia stages. This phenomenon desveres further investigation and it is suggested to be associated to glial/inflammatory or compensatory neuronal responses. Here,...

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 rati...

Background Classical literature has pointed at lateralization of the relationship between memory scores and cerebral hemisphere injury. Epilepsy studies have suggested an association between left hippocampal damage and verbal memory deficits, and between right hippocampal damage and visual memory deficits. We aimed to explore this concept in the co...

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...

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 f...

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...

Background In‐vivo PET imaging studies have demonstrated neuroinflammation (microglia reactivity) in the neocortex of Alzheimer’s disease (AD) patients. However, the extent and implication of microglia reactivity in white matter regions remains unclear. Here, we explored microglia reactivity in white matter using PET imaging of the translocator pro...

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 t...

Background Long COVID is an under‐characterized disorder that affects a wide range of individuals after COVID‐19 resolution. Long COVID individuals report persistent neurological manifestations, such as anxiety. Understanding its effects in the brain might help uncover the actual burden imposed by the pandemic sequelae and either define or discard...

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 eva...

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 as...

Background It is feasible to train a model on a healthy cohort to estimate the chronological age from a T1‐weighted (T1w) MRI. This model can be used to estimate the apparent brain age of subjects with Alzheimer's Disease (AD). The difference between the true chronological age and the apparent brain age, called Brain Age Gap (BAG), is a potential f...

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 Partici...

Background Utilizing PET amyloid‐beta (Aß) 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...

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‐ß (Aß) plaque load, but low tau accumulation, suggesting that this single‐nucleotide polymorphism (SNP) in RELN conferred a resilience not only t...

Background PET biomarkers have proven valuable for identifying cognitively unimpaired (CU) individuals at‐risk of near‐term clinical progression. Given the increasing interest in plasma biomarkers to detect Alzheimer’s pathology, we assessed levels of amyloid (Aß42/40) and tau (p‐tau217 and p‐tau181) biomarkers in plasma (A+T+plasma) in CU individu...

Background Long‐COVID is characterized by persistent symptoms post‐infection with SARS‐CoV‐2. This condition includes neurological manifestations and has been proposed as a potential risk factor for the development of dementia. Individuals presenting with dementia due to Alzheimer's disease have dysfunctional brain metabolism, including metabolic b...

Background While we know dementia in Alzheimer’s disease (AD) results from the accumulation of ß‐amyloid (Aß), tau pathology, and hippocampus atrophy (HC), it is still unclear how these factors impose cognitive decline. Method We used Structural Equation Models (SEM; lavaan R package) to explore the complex relationships between the neurobiologica...

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 v...

Background The default‐mode network (DMN) consists of brain regions with higher resting activity levels. Amyloid‐ß (Aß) deposition in Alzheimer’s disease (AD) occurs predominantly throughout the DMN, suggesting that activity within the network may facilitate disease processes. Indeed, increased neural activity is positively associated with Aß produ...

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 gyru...

Background Increased uptake on Tau positron‐emission tomography (PET) is sometimes observed in the absence of amyloid ß accumulation. This A‐T+ PET profile might represent primary age‐related tauopathy (PART), an amyloid ß‐independent 3R/4R tauopathy observed in aging brains. Although A‐T+ individuals have been shown to follow a different cognitive...

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 observ...

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. Method We included 92 indiv...

Background Glial reactivity is a key phenomenon in Alzheimer’s disease (AD) and is closely associated with amyloid‐ß (Aß) pathology. Although compelling experimental data suggest that microglial activation modulates reactive astrogliosis, it remains to be elucidated whether microglial activation influences the association of Aß pathology with react...

Background Alzheimer’s disease is a neurodegenerative disease associated with the accumulation of Amyloid‐ß and Tau neurofibrillary tangles following a pattern known as Thal and Braak stages, respectively (Thal 2002; Braak 1995,2011). Recent research (Pascoal 2020) showed the possibility of recapitulating Braak’s histopathological stages in vivo us...

Background Glutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic and metabotropic receptors, such as the neuronal metabotropic glutamate receptor 5 (mGluR5). The radiotracer [11C]ABP688 binds allosterically to the mGluR5, providing a valuable tool to understand glutamatergic function. We have previously shown tha...

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 Im...

Background Lewy bodies (LB), the main hallmark of Parkinson’s disease (PD), are a frequent co‐pathology in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). The varying extents of LB pathology in these disorders can influence disease progression and severity. Consequently, understanding LB impact on the proteomic profile of these diseas...

Background The deposition of β‐amyloid (Aβ) plaques is a classical neuropathological feature of Alzheimer’s disease (AD). Currently, it is believed that intermediate products of the Aβ fibrillogenesis process, like the β‐amyloid oligomers (AβOs), are the most toxic forms, and are involved in neurodegenerative processes in AD. The evaluation of cere...

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 neurof...

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 pTa...

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 cli...

Background Alzheimer's disease is characterized by the accumulation of amyloid beta and the formation of tau neurofibrillary tangles (NFTs), leading to irreversible neurodegeneration. The formation of NFTs is believed to follow a stereotypical pattern known as Braak stages. Here, using tau‐PET tracer 18F‐MK‐6240 we aim to analyze patterns of Tau ac...

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 cognitivel...

Background Anti‐amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid‐ and tau‐positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine‐learning prediction model to identify tau positivity in amyloid‐positive individuals using clinical...

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...

Background An accurate prediction of Alzheimer’s disease (AD) progression is important for patient management and optimization of participant selection for trials. Here, we compared and combined plasma p‐tau217 and tau‐PET measures for predicting longitudinal cognitive decline and clinical progression in cognitively unimpaired participants. Method...

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 A...

Background Glutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic and metabotropic receptors, such as the neuronal metabotropic glutamate receptor 5 (mGluR5). The radiotracer [¹¹C]ABP688 binds allosterically to the mGluR5, providing a valuable tool to understand glutamatergic function. We have previously shown tha...

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...

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. Method We included 92 indiv...

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 D...

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...

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...

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...

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 observ...

Background Alzheimer’s disease is a neurodegenerative disease associated with the accumulation of Amyloid‐β and Tau neurofibrillary tangles following a pattern known as Thal and Braak stages, respectively (Thal 2002; Braak 1995,2011). Recent research (Pascoal 2020) showed the possibility of recapitulating Braak's histopathological stages in vivo us...

Background Screen failure due to amyloid negativity is yet a problem in clinical trials for anti‐amyloid drugs. In this context, clinical characteristics of patients presenting with cognitive decline may decrease the screen failure ratio by increasing the odds of selecting individuals with brain amyloid pathology. Herein, we aimed at estimating amy...

Background PET biomarkers have proven valuable for identifying cognitively unimpaired (CU) individuals at‐risk of near‐term clinical progression. Given the increasing interest in plasma biomarkers to detect Alzheimer’s pathology, we assessed levels of amyloid (Aβ42/40) and tau (p‐tau217 and p‐tau181) biomarkers in plasma (A+T+plasma) in CU individu...

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 v...

Background The default‐mode network (DMN) consists of brain regions with higher resting activity levels. Amyloid‐β (Aβ) deposition in Alzheimer’s disease (AD) occurs predominantly throughout the DMN, suggesting that activity within the network may facilitate disease processes. Indeed, increased neural activity is positively associated with Aβ produ...

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 f...

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 t...