Guilherme Bauer-Negrini

• PhD
• Postdoctoral Associate at University of Pittsburgh

Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute...

Autism spectrum disorder (ASD) is characterized by impairments in both social communication and interaction and repetitive or stereotyped behaviors. Although its etiology remains unknown, genetic and environmental risk factors have been associated with this disorder, including the exposure to valproic acid (VPA) during pregnancy. Resveratrol (RSV)...

Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic system has been associated with the o...

Background and objective Circular RNAs (circRNAs) are endogenous molecules of non-coding RNA that form a covalently closed loop at the 3′ and 5′ ends. Recently, the role of these molecules in the regulation of gene expression and their involvement in several human pathologies has gained notoriety. The identification of circRNAs is highly dependent...

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition estimated to affect 1% of individuals worldwide. Its etiology is still not fully understood, but several molecular alterations in ASD are related to noncoding RNAs (ncRNAs). Recently, gene expression of circular RNAs (circRNAs) has been shown to be altered in the brains of...

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 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 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 (Aß), neurofibrillary tau tangles, and cognitive decline. Longitudinal studies confirmed its abil...

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 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 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 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 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 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 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 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 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 Blood‐based biomarkers for Alzheimer’s disease (AD) are increasingly prevalent and accessible beyond research environments. Consequently, it is crucial to determine whether confounding factors, particularly highly prevalent comorbidities, influence the levels of these blood biomarkers, thereby refining their clinical interpretation. In t...

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 Multiple studies have linked high cortisol levels, a frequently used biomarker of stress, with the Alzheimer's disease (AD) pathophysiology. However, the relationship between cerebrospinal fluid (CSF) cortisol levels and AD‐related brain atrophy is not fully understood. This study sought to investigate the cross‐sectional and longitudina...

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 Blood‐based biomarkers for Alzheimer’s disease (AD) are increasingly prevalent and accessible beyond research environments. Consequently, it is crucial to determine whether confounding factors, particularly highly prevalent comorbidities, influence the levels of these blood biomarkers, thereby refining their clinical interpretation. In t...

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 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 abil...

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 Multiple studies have linked high cortisol levels, a frequently used biomarker of stress, with the Alzheimer's disease (AD) pathophysiology. However, the relationship between cerebrospinal fluid (CSF) cortisol levels and AD‐related brain atrophy is not fully understood. This study sought to investigate the cross‐sectional and longitudina...

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 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...

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...

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 bi...

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 a...

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 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 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 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 The newly proposed criteria by the AA working group incorporates both biological and clinical stages to characterize the progression of AD. In this study, we aim to evaluate the agreement between these two complementary systems. Methods Using 188 participants from McGill TRIAD and 139 from the HEAD cohorts, we categorized participants i...

Background Recent studies have shown that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). Increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with a more severe AD presentation, including...

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 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 Aβ pathology and mediates tau‐p...

Background Dysregulation of cholesterol metabolism contributes to the increase of cerebral vascular diseases, favoring the development of dementia. In this sense, high levels of high‐density lipoprotein (HDL) are considered protective against the outcomes associated with cardiovascular diseases. However, little is known about the effect of plasma H...

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...

Previous studies have shown that glial and neuronal changes may trigger synaptic dysfunction in Alzheimer’s disease(AD). However, the link between glial and neuronal markers and synaptic abnormalities in the living brain is poorly understood. Here, we investigated the association between biomarkers of astrocyte and microglial reactivity and synapti...

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication and social interaction, and presence of repetitive behaviors, and restricted interests. Many structural and functional brain alterations can be observed in individuals with ASD. Therefore, functional magnetic resonance imaging (fMRI) has been...

Background The relationship between high cortisol levels and brain atrophy in patients across the Alzheimer’s disease (AD) continuum has been relatively unexplored. Thus, this study sought to investigate the association between plasma cortisol levels and brain cortical thickness in patients across the biological and clinical continuum of AD. Metho...

Background Deep learning models, particularly convolutional neural networks (CNNs), have shown promise in Alzheimer’s disease (AD) classification using tau PET data. However, limited sample sizes and unharmonized tau tracers present challenges to developing an agnostic tau tracer tool to predict AD using machine learning. Transfer learning, which l...

Background Multiple studies have linked high cerebrospinal fluid (CSF) cortisol levels, a frequently used biomarker of stress, with the Alzheimer’s disease (AD) pathophysiology. However, the relationship between CSF cortisol levels and AD‐related brain atrophy is not fully understood. Thus, this study sought to determine the association between CSF...

Subjective cognitive decline (SCD) is defined as a memory complaint in individuals without an objective measure of cognitive impairment. In this study, we investigated the morphometric and metabolic brain changes in individuals presenting with SCD. Age and sex matched structural MRI and [18F]FDG PET images from SCD and CU (n = 101, per group) were...

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue...

Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumor grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) altera...

Autism Spectrum Disorder can present a plethora of clinical conditions associated with the disorder, such as greater brain volume in the first years of life in a significant percentage of patients. We aimed to evaluate the brain water content, the blood-brain barrier permeability, and the expression of aquaporin 1 and 4, and GFAP in a valproic acid...

Impairments in social behaviour are a defining feature of autism spectrum disorder (ASD). Individuals with ASD also usually present some difficulty to recognise or understand another person’s feelings. Therefore, it is possible that altered empathy processing could hinder typical social interaction in ASD. Recently, robust paradigms confirmed that...

Objective: Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA). Pregnant Swiss mice received a single intraperitoneal injection of 600 mg/kg of VPA (VPA gro...

This article contains data of Social Transmission of Food Preference in an animal model of autism and the evaluation of a set of microRNA analyzed in autistic patients and animal model of autism. The analyses of the absolute consumption of two flavored food by male rats prenatally exposed to valproic acid (VPA) and treated with resveratrol (RSV), s...