Pedro Rosa

McGIll UNiversity, Douglas Mental Health University Institute · Neurology & Neurosurgery and Psychiatry

Background The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio. Methods An international group of experts was est...

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer’s disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD...

Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-te...

Background Pathogenic prion protein may start to deposit in some brain regions and cause functional alterations in the asymptomatic stage in Creutzfeldt–Jakob disease. The study aims to determine the trajectory of the brain metabolic changes for prion protein diseases at the preclinical stage. Methods At baseline, we enrolled five asymptomatic PRN...

Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the...

Abnormalities in the expression of metabotropic glutamate receptor type 5 (mGluR5) have been observed in the hippocampus of patients with drug-resistant mesial Temporal Lobe Epilepsy (mTLE). Ex-vivo studies in mTLE hippocampal surgical specimens have shown increased mGluR5 immunoreactivity, while in vivo whole brain imaging using positron emission...

Background The integrity and function of catecholamine neurotransmitter systems can be assessed using MRI sequences often referred to as neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. To support such futu...

Background Synaptic dysfunction and degeneration are central to Alzheimer’s disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better unde...

Purpose Advances in functional imaging allowed us to visualize brain glucose metabolism in vivo and non-invasively with [¹⁸F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging. In the past decades, FDG-PET has been instrumental in the understanding of brain function in health and disease. The source of the FDG-PET signal has bee...

Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [¹⁸F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTa...

For many years Alzheimer’s disease (AD) was associated with the dementia stage of the disease, the tail end of a pathophysiological process that lasts approximately two decades. Whereas early disease staging assessments focused on progressive deterioration of clinical functioning, brain imaging with positron emission tomography (PET) and cerebrospi...

Background: PET imaging of [ ¹¹ C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [ ¹¹ C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Metho...

Introduction [ ¹⁸ F]MK6240 is a tau-PET tracer that quantifies brain tau neurofibrillary tangles (NFT) load in Alzheimer’s disease (AD). The aims of our study are to test the stability of common reference regions estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention in the longit...

Well-authenticated biomarkers can provide critical insights into the biological basis of Alzheimer disease (AD) to enable timely and accurate diagnosis, estimate future burden and support therapeutic trials. Current cerebrospinal fluid and molecular neuroimaging biomarkers fulfil these criteria but lack the scalability and simplicity necessary for...

Background Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and inv...

Background Studies exploring topological properties of the metabolic network during the presymptomatic stage of genetic frontotemporal dementia (FTD) are scarce. However, such knowledge is important for understanding brain function and disease pathogenesis. Therefore, we aimed to explore FTD-specific patterns of metabolism topology reconfiguration...

Background Attention-Deficit/Hyperactivity Disorder (ADHD) persists in older age and is postulated to be a risk factor for cognitive impairment and Alzheimer’s Disease (AD). However, this notion relies exclusively on epidemiological associations, and no previous study has linked ADHD with a decline in cognitive performance in older adults or with A...

Introduction: Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for...

Background Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organization and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and met...

Introduction In Alzheimer’s disease clinical research, glial fibrillary acidic protein (GFAP) released in the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was recently demonstrated that plasma GFAP levels are associated with amyloid-β (Aβ) but not tau pathology. The molecular un...

Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and neuropsychiatric disorders. [11C]Martinostat allows in vivo quantification of class I/IIb HDACs and may be useful for the quantification of drug‐occupancy relationship, facilitating d...

Introduction Plasma amyloid-β (Aβ), phosphorylated tau (p-tau), and glial fibrillar acid protein (GFAP) can identify Alzheimer’s disease (AD) pathophysiology with high accuracy. However, comparing their performance in the same individuals remains under-explored. Methods We compared the predictive performance of plasma Aβ42/40, p-tau(at threonine 1...

Background Tau in Alzheimer's disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [¹⁸F]MK6240 tau-PET, plasma pTau181 and pTau231. Methods We assessed cog...

SARS‐CoV‐2 infection can damage the nervous system with multiple neurological manifestations described. However, there is limited understanding of the mechanisms underlying COVID‐19 neurological injury. This is a cross‐sectional exploratory prospective biomarker cohort study of 21 patients with COVID‐19 neurological syndromes (Guillain Barre Syndro...

Background Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (Aβ) positivity as determined b...

The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer’s disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-MRI). We examined whether integrity of the LC-norepinephrine system, assessed with NM-MRI, is associated with stage of AD and with neuropsychi...

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD...

Recent studies suggest a framework where white matter (WM) atrophy plays an important role in fronto-temporal dementia (FTD) pathophysiology. However, these studies often overlook the fact that WM tracts bridging different brain regions may have different vulnerabilities to the disease and the relative contribution of GM atrophy to this WM model, r...

Background Abnormal mitochondrial metabolism has been described in Alzheimer’s disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study is to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggregation, or glucose metabolism...

Understanding whether vascular risk factors synergistically potentiate Alzheimer's disease progression is important in the context of emerging treatments for preclinical Alzheimer's disease. The existence of a synergistic relationship could suggest that the combination of therapies targeting Alzheimer's disease pathophysiology and vascular risk fac...

Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns,...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develo...

The development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS...

Hyperphosphorylation of tau is responsible for its loss of normal physiological function, gain of toxicity and its aggregation to form NFTs. Increased phosphorylated tau is detected in Alzheimer´s disease (AD) CSF and blood, and changes in the tau phosphorylation pattern may reflect different stages of the disease progression. A better understandin...

Cognitive reserve (CR), a protective mechanism, allows for sustained cognitive functioning in older adults with greater experiential resources. Bilingualism, an indicator of greater cognitive reserve, has been found to preserve cognitive performance in older adults despite significant disease pathology. While the association with amyloid has been w...

We examine the role of CSF apolipoprotein B (apoB) as a putative indicator of early tau pathology in pre‐symptomatic Alzheimer’s disease (AD). Among 129 cognitively unimpaired elderly at increased risk of AD (PREVENT‐AD cohort), we assessed blood and cerebrospinal fluid apoB, apoC3 and apoE protein levels using the the Milliplex APOMAG‐62k human ap...

Alzheimer’s disease (AD) was biologically defined by the 2018 NIA‐AA Research Framework (RF), which recommends dichotomously categorizing biomarker status as normal or abnormal using single cutpoints. Nevertheless, the RF also states a three‐range approach might be useful in AD research. However, this potentially relevant strategy remains mostly un...

Recent studies have shown that pathological amyloid deposition and tau accumulation, hallmarks of the Alzheimer's disease, are closely related to cognitive deficits in older individuals. The present study evaluates the associations between the Alzheimer's disease hallmarks and verbal fluency and lexical speed access impairment. The study was conduc...

Pathophysiological detection of Alzheimer’s disease (AD) is commonly made using cerebrospinal fluid (CSF) and positron emission tomography (PET). However, these methods are invasive and expensive, limiting their use in clinical settings Blood‐based biomarkers, mainly measuring phosphorylated tau epitopes at threonine 181 (p‐tau181), threonine 217 (...

Following the rapid spread of the COVID‐19 virus throughout Quebec, the TRIAD cohort, a longitudinal observational study, evaluated the effects of COVID‐19 on it’s aging and vulnerable population and their caregivers. This study aims at investigating the behavioural and psychological effects of COVID‐19 and social isolation on the aging population....

The occurrence of the COVID‐19 pandemic has had a significant impact on cohort studies, particularly those whose subjects are at higher risk of developing complications from the virus. As such, assessment methods must be adapted to minimize COVID‐19 exposure risk. The TRIAD (Translational Biomarkers of Aging and Dementia) cohort assessed N=292 indi...

Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation. Several studies have highlighted the link between systemic inflammation and the Alzheimer’s disease (AD) pathophysiology. In fact, experiments with animal models and studies with AD patients demonstrated the hyperactivation of neutrophils a...

We examine the role of brain apolipoprotein B (apoB) as a putative CSF indicator of early tau pathology in pre‐symptomatic Alzheimer’s disease (AD). Among 129 cognitively unimpaired elderly at increased risk of AD (PREVENT‐AD cohort), we assessed blood and cerebrospinal fluid apoB, apoC3 and apoE protein levels with those of amyloid β42, total tau...

As the only optically accessible part of the central nervous system, the retina represents an intriguing opportunity for the detection of biomarkers for Alzheimer’s disease (AD). This study evaluated the performance of the Retinal Deep PhenotypingTM platform, a digital biomarker platform comprising a hyperspectral retinal camera and image analysis...

Deposition of amyloid‐beta (Aβ) plaques and hyperphosphorylated tau are known hallmarks of Alzheimer’s disease (AD). In addition, neuroinflammation or microglia activation plays a role in Alzheimer’s pathophysiology and may be a potential driver of abnormal tau deposition. This study demonstrated the important brain regions where microglia activati...

While the global COVID‐19 pandemic has hindered many human research operations, it has allowed for the investigation of novel scientific questions. Particularly, the effects of the pandemic and its resulting social isolation on elderly individuals and their association with Alzheimer’s disease biomarkers remains a broad and open question. Here, we...

Blood phosphorylated tau (p‐tau) has proven to be the primary candidate as an accessible and scalable biomarker for Alzheimer’s disease (AD). Both p‐tau181 and p‐tau217 are highly accurate to detect AD within dementia cases. Our recent work in cerebrospinal fluid, however, indicates p‐tau231 to be associated to incipient AD pathology. In light of t...

The natural history of Alzheimer’s disease (AD) comprises a long preclinical stage characterized by pathological changes that start decades before symptoms arise. Despite that AD is defined based on the presence of amyloid‐β (Aβ) and tau pathology, increasing evidence supports neuroinflammation as one of the earliest pathomechanistic alterations th...

Assessments of tau usually come from cerebrospinal fluid or Positron Emission Tomography (PET). However, those methods are expensive and not readily available. Current research is focusing on cost‐effective blood‐based biomarkers, and a novel immunoassay for plasma pTau181 has been created. Even though there are strong associations between plasma p...

By obtaining a better grasp on the impact of the COVID‐19 pandemic on individuals with cognitive impairment, this knowledge could be used to improve the delivery of information to this particular group. We aimed to assess the relationship between tau deposition and the change in anxiety levels, before and during the pandemic. We hypothesized that s...

Speaking two or more languages has been shown to contribute to cognitive reserve and to delay the onset of Alzheimer’s disease (AD). However, little is known about the effect of bilingualism on the progression of AD biomarkers. In this study, we intended to investigate the effect of bilingualism on cognitive scores and on AD biomarkers in a cohort...

In the context of Alzheimer’s disease (AD), tau pathology is a major driver of the neurodegenerative cascade that ultimately leads to loss of neurons and synapses. In fact, studies have shown that neurodegeneration is more strongly associated with tau pathology than amyloid‐β (Aβ) accumulation. Although plasma neurofilament light (NfL) is a neuroax...

Recent developments in the biomarker field allow Alzheimer’s disease (AD) pathophysiology to be reflected at the preclinical stage. We recently presented an assay targeting tau fragments ending at residue 368, which exhibited a stage‐wise decrease in a ratio with total‐tau. The tau368/T‐tau ratio also correlated with tau positron emission tomograph...

Tau is usually assessed through cerebrospinal fluid or Positron Emission Tomography (PET). However, those methods are expensive and not readily available. Research is now focusing on cost‐effective blood‐based biomarkers to assess Alzheimer’s disease (AD) pathophysiologies. A novel immunoassay for plasma pTau181 has been created, and even though th...

The Aggie Figures Learning Test (AFLT) is a visual memory assessment tool, constructed as an analog to the Rey Auditory Verbal Learning Test (RAVLT). The AFLT includes three sequences of abstract drawings as stimuli –a primary set which is repeated across five trials, an interference set, and a recognition set. After about twenty minutes, the test...

Aggie Figures Learning Test (AFLT) is a visual memory test that was conceived as an analogue of the widespread Rey Auditory Verbal Learning Test (RAVLT), which tests verbal memory. Previous research has indicated that performance may rely on the left medial temporal lobe (lMTL) for RAVLT and on the right medial temporal lobe (rMTL) for AFLT, althou...

Individuals with cognitive/memory impairments may be more vulnerable to COVID19 due to having poor knowledge of COVID19 and how to protect themselves under current policies. Here, we aimed to show cognitive/memory impairment is associated with less knowledge or less anxiety change related to COVID19. We hypothesized that the effect of hippocampal v...

Decline in executive function has been noted to precede other forms of cognitive decline in the prodromal stage of Alzheimer’s disease (Clark et al., 2011). The D‐KEFS Color‐Word Interference test (CWIT) is a cognitive test that measures executive function across several conditions. Few studies have explored the relationship between tau deposition...

Deposition of amyloid‐beta (Aβ) plaques and hyperphosphorylated tau are known hallmarks of Alzheimer’s disease (AD). In addition, neuroinflammation or microglia activation plays a role in AD pathophysiology and may be a potential driver of abnormal tau deposition. This study demonstrated the important brain regions where microglia activation, in ad...

Compelling experimental evidence suggests that microglial activation is involved in the spread of tau neurofibrillary tangles over the neocortex in Alzheimer’s disease (AD). Here, we tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak‐like pattern in the human brain. We studied 130...

Background: Contactins are a family of molecules that are involved in neuronal development. Contactin 5 (CNTN5) is a neuronal membrane protein that contributes to axonal targeting, synaptic formation and plasticity. A GWAS performed in a population isolate from Eastern Canada identified a polymorphism in the CNTN5 gene (rs1461684_G) which is assoc...

Background: Monitoring pathophysiological stages of Alzheimer's Disease (AD) is important for understanding, forecasting and ultimately treating the disease. One prominent example of such staging is the spread of tau protein manifested in the stage-wise accumulation of neurofibrillary tangles [1]. With the development of high-affinity tau PET trac...

The common marmoset has emerged as a popular model in neuroscience research, in part due to its reproductive efficiency, genetic and neuroanatomical similarities to humans and the successful generation of transgenic lines. Stereotaxic procedures in marmosets are guided by 2D stereotaxic atlases, which are constructed with a limited number of animal...

Objectives The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β 1-42 (Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer’s disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use ass...

Background: PET imaging of [ ¹¹ C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [ ¹¹ C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Metho...