Renaud La Joie

• PhD
• PostDoc Position at University of California, San Francisco

Introduction. Subjective cognitive decline (SCD) could help identify early stages of Alzheimer’s disease. However, SCD is multidetermined and protean, and the type of cognitive complaint associated with preclinical Alzheimer’s needs refinement. Methods. 185 Non-demented elders recruited from either the community or from a memory clinic filled out a...

INTRODUCTION. Subjective cognitive decline (SCD) could indicate preclinical Alzheimer’s disease but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questio...

Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vul...

Alzheimer's disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge...

Gray matter atrophy, glucose hypometabolism, and β-amyloid Aβ deposition are well-described hallmarks of Alzheimer's disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimer's disease. Structural magnetic resonance imaging, (18)F-fluorodeoxyglucose...

Background and objectives: Evaluating tau biomarkers in patients with available autopsy data is critical for validating their sensitivity and specificity to detect Alzheimer's disease neuropathologic changes (ADNC). We examined the association between tau-PET (using [18F]Flortaucipir), plasma ptau-217, and measures of AD neuropathology in a group o...

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields...

INTRODUCTION List-learning tasks are important for characterizing memory in ADRD research, but the Uniform Data Set neuropsychological battery (UDS-NB) lacks a list-learning paradigm; thus, sites administer a range of tests. We developed a harmonized memory composite that incorporates UDS memory tests and multiple list-learning tasks. METHODS: Item...

Importance Detection bias occurs when an exposure is associated with a systematic difference in outcome ascertainment or diagnosis. For dementia research, diagnosed health conditions that bring patients into frequent interaction with health care may increase the chance that an individual receives a dementia diagnosis. Objective To evaluate potenti...

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred n...

Amyloid‐β (Aβ) positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarkers are now established tools in the diagnostic workup of patients with Alzheimer's disease (AD), and their use is anticipated to increase with the introduction of new disease‐modifying therapies. Although these biomarkers are comparable alternatives in r...

Background Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated ¹⁸ F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) ³ H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo ¹⁸ F-MK-6240 tau PET study in former American football playe...

Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal atrophy was thought to result from tau tangles in AD, different neuropathologies can lead to hippocampal atrophy, especially TAR DNA‐binding protein 43 (TDP‐43) pathology. In this narrative review, we evaluate existing studies...

INTRODUCTION Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers. METHODS We thoroughly investigated the ability of various machine learning models to predict clinically useful tau‐PET compos...

INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized co...

Background: As literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials. Objectives: The current...

Importance Blood-based biomarkers for Alzheimer disease (AD) are clinically available, but their value is not well understood in syndromes typically associated with frontotemporal lobar degeneration syndromes (FTLD). Objective To investigate the clinical importance and detectability of AD in FTLD-related neurodegenerative syndromes using 3 plasma...

Background The clinical presentations of early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) described EOAD as predominantly amnestic, though this p...

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 The variability in the regional distribution of Aß‐PET signal and its relation to clinical features is debated. We used data‐driven approaches to uncover heterogeneity in cortical Aß‐PET signal from a large representative sample collected through the IDEAS study. Methods We analysed cross‐sectional Aß‐PET collected from 10,361 patients...

Background Understanding how early‐onset Alzheimer’s disease (EOAD) differs from typical late‐onset AD (LOAD) is an important goal of AD research that may help increase the sensitivity of unique biomarkers for each phenotype. Building upon prior work based on small samples, here we leveraged two large, well‐characterized natural history study cohor...

Background The relationship between tau pathology and cognition as a function of age and whether these relationships are consistent across samples is unknown. A growing number of studies now perform positron emission tomography with tau ligands (tau‐PET), making it possible for an improved understanding of the dynamics of tau and cognition in relat...

Background Large‐scale studies comparing sporadic early‐onset AD (EOAD, age<65) and late‐onset AD (LOAD, age = 65) are lacking. We compared amyloid‐PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early‐Onset AD Study (LEADS) and the Alzheimer’s...

Background Medial temporal lobe (MTL) atrophy is an early feature of multiple neurodegenerative diseases. In genetic frontotemporal lobar degeneration (FTLD, i.e. individuals carrying GRN, MAPT, or C9orf72 mutations), MTL atrophy can occur 10‐15 years before symptom onset. We aimed to better characterize MTL atrophy patterns in presymptomatic and s...

Background The timing of tau‐PET accumulation and cognitive decline in sporadic early‐onset Alzheimer’s disease (eoAD, age‐at‐onset<65) has not been established and is needed to optimize tau‐PET as an outcome measure in clinical trials. Here we leverage large‐sample, longitudinal data from the Longitudinal Early‐onset Alzheimer’s Disease Study (LEA...

Background Diagnosing sporadic early‐onset AD (EOAD, age‐at‐onset<65) is challenging: in the multi‐center Longitudinal Early‐onset Alzheimer’s Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid‐PET‐negative. Here we used FDG‐PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify...

Background The medial temporal lobe (MTL) has distinct cortical subregions that are differentially vulnerable to pathology and neurodegeneration in diseases such as Alzheimer’s disease. However, previous protocols for segmentation of MTL cortical subregions on magnetic resonance imaging (MRI) vary substantially across research groups, and have been...

Background Previous studies on sex differences in amyloid burden have shown inconsistent findings. We examined the effect of sex on amyloid‐PET outcomes in a large, real‐world, cohort of individuals with cognitive impairment. Method The IDEAS study evaluated the clinical utility of amyloid‐PET in 18,295 Medicare beneficiaries age ≥65 years with MC...

Background Large‐scale studies comparing sporadic early‐onset AD (EOAD, age<65) and late‐onset AD (LOAD, age≥65) are lacking. We compared amyloid‐PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early‐Onset AD Study (LEADS) and the Alzheimer’s D...

Background Medial temporal lobe (MTL) atrophy is an early feature of multiple neurodegenerative diseases. In genetic frontotemporal lobar degeneration (FTLD, i.e. individuals carrying GRN, MAPT, or C9orf72 mutations), MTL atrophy can occur 10‐15 years before symptom onset. We aimed to better characterize MTL atrophy patterns in presymptomatic and s...

Several new blood‐based biomarkers (BBMs) of Alzheimer’s disease and related neuropathologies have completed late‐stage validation and are beginning to be used in the clinical setting. However, the role of BBMs in various clinical settings, especially their specific context‐of‐use, remains an open question for the field. Several studies are beginni...

Background The variability in the regional distribution of Aβ‐PET signal and its relation to clinical features is debated. We used data‐driven approaches to uncover heterogeneity in cortical Aβ‐PET signal from a large representative sample collected through the IDEAS study. Methods We analysed cross‐sectional Aβ‐PET collected from 10,361 patients...

Background The timing of tau‐PET accumulation and cognitive decline in sporadic early‐onset Alzheimer’s disease (eoAD, age‐at‐onset<65) has not been established and is needed to optimize tau‐PET as an outcome measure in clinical trials. Here we leverage large‐sample, longitudinal data from the Longitudinal Early‐onset Alzheimer’s Disease Study (LEA...

Background Collection, storage, and distribution of human fluid biospecimens in a scientifically rigorous manner is challenging. It requires physical space availability and robust infrastructure. Nonetheless, it is key to contribute to research in Alzheimer’s Disease and Related Disorders, including Frontotemporal Dementia (FTD). These specimens fa...

Background Understanding how early‐onset Alzheimer’s disease (EOAD) differs from typical late‐onset AD (LOAD) is an important goal of AD research that may help increase the sensitivity of unique biomarkers for each phenotype. Building upon prior work based on small samples, here we leveraged two large, well‐characterized natural history study cohor...

Background The relationship between tau pathology and cognition as a function of age and whether these relationships are consistent across samples is unknown. A growing number of studies now perform positron emission tomography with tau ligands (tau‐PET), making it possible for an improved understanding of the dynamics of tau and cognition in relat...

Background The Centiloid framework was developed to harmonize amyloid‐PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid‐PET scans from the largest “real‐world” study of amyloid‐PE...

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 Diagnosing sporadic early‐onset AD (EOAD, age‐at‐onset<65) is challenging: in the multi‐center Longitudinal Early‐onset Alzheimer’s Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid‐PET‐negative. Here we used FDG‐PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify...

Background With the emergence of Alzheimer's disease (AD) disease‐modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid‐β (Aβ) plaques and tau tangles. Method Plasma %p‐ta...

Background Tau‐PET with [18F]Flortaucipir is FDA‐approved for the identification of AD tau neuropathology in the differential diagnosis of patients with cognitive impairment. However, its performance in detecting early AD stages requires further assessment. We aimed to i) examine the relationships between Flortaucipir‐PET and AD neuropathology, and...

Background The Uniform Data Set (UDS) neuropsychological battery, administered across Alzheimer’s Disease Centers (ADC), includes memory tests but lacks a list‐learning paradigm. ADCs often supplement the UDS with their own preferred list‐learning task. Given the importance of list‐learning for characterizing memory, we aimed to develop a harmonize...

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early‐onset dementia. METHODS Data from 307 cognitively normal (CN) volunteer participants and those with...

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller‐scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS Z‐score cognitive‐domain composites for 311 am...

Background In the era of disease‐modifying treatments for Alzheimer's disease (AD), accurate detection of underlying AD pathology is critical. Blood‐based biomarkers for AD are increasingly available, but their diagnostic performance is not well‐understood across the spectrum of neurodegenerative disease, especially when AD presents as co‐pathology...

Amyloid‐PET quantification through the tracer‐independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid‐β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context‐of‐use recommend...

Amyloid-PET detects fibrillar β- amyloid deposits, a defining feature of Alzheimer's disease. This technology has been used in research for over 20 years, and is now used in clinical practice to guide patient diagnosis and management. However, the real-world use of amyloid-PET may differ from research settings due to less standardized acquisition p...

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors a...

INTRODUCTION Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated. METHODS We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD a...

Introduction Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health. Methods We used baseline data from 282...

Importance An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. Objective To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. Design, Setting, and Participants Thi...

Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, commonly used in Alzheimer’s disease (AD) research and clinical trials. However, its routine clinical use is limited by cost and accessibility barriers. Here we explore using machine learning (ML) models to predict...

Approximately 5% of Alzheimer’s disease patients develop symptoms before age 65 (early-onset Alzheimer’s disease), with either sporadic (sporadic early-onset Alzheimer’s disease) or dominantly inherited (dominantly inherited Alzheimer’s disease) presentations. Both sporadic early-onset Alzheimer’s disease and dominantly inherited Alzheimer’s diseas...

Introduction: We comprehensively evaluated how self- and informant-reported neuropsychiatric symptoms (NPS) were differentially associated with cerebral amyloid-beta (Aβ) PET levels in older adults without dementia. Methods: Two hundred and twenty-one participants (48% female, age = 73.4 years ± 8.4, Clinical Dementia Rating = 0 [n = 184] or 0.5...

Background and objectives: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and cli...

Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and...

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain‐wide association approach in the MRI substudy of UK Biobank ( N = 41,964; mean...

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical scho...

With the emergence of Alzheimer’s disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217...

Introduction Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four‐repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum—AD showing reduced wake...

INTRODUCTION With emergence of disease‐modifying therapies, efficient diagnostic pathways are critically needed to identify treatment candidates, evaluate disease severity, and support prognosis. A combination of plasma biomarkers and brief digital cognitive assessments could provide a scalable alternative to current diagnostic work‐up. METHODS We...

INTRODUCTION We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle‐aged and older adults. METHODS Among 45,616 dementia‐free participants aged 45–80, linear regressions tested whether genetic risk score for AD (AD‐GRS) had age‐dependent associations with 38 regional brain magnetic reson...

INTRODUCTION The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co‐organized and co‐sponsored by the Alzheimer's Association,...

Background Through studies of animal heterochronic parabiosis (fusion of juvenile and older adult animal circulatory systems), growth differentiation factor 11 (GDF11) has been identified as a blood rejuvenation factor that can promote neurogenesis, vascular remodeling, and memory improvement in the presence of age‐related declines. However, it is...

Background Few prior studies have investigated whether genetic risk for Alzheimer’s disease (AD) can manifest through altered neurodevelopment of AD‐vulnerable brain regions. This pre‐registered study tests the effects of AD polygenic risk on morphometric neurodevelopment across 3 large datasets totaling 8,364 youths aged 3‐22 (Table 1) Method Pol...

Background The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and a hotspot of neurodegenerative processes (e.g., accumulation of tau tangles or TDP‐43). Importantly, the MTL cortex comprises several subregions with distinct functional, cytoarchitectonic, and macro‐anatomical features (Fig. 1). In vivo...

Background Discordance between the clinical diagnosis of AD by experts after a comprehensive evaluation and AD pathology on autopsy remains common. We sought to identify clinical situations where amyloid‐PET would be most valuable as a diagnostic tool by identifying predictors associated with discordance between initial clinical diagnosis and amylo...

Background We aimed to describe amyloid‐ and tau‐PET in patients with sporadic Early Onset AD (sEOAD) from the Longitudinal Early‐onset Alzheimer’s Disease Study. We focused on amyloid‐tau relationships and on the association between i) age, sex, and ii) cross‐sectional and longitudinal PET measures. Methods In December 2022, we selected patients...

Background The longitudinal progression of tau pathology in sporadic early‐onset Alzheimer’s disease (EOAD, age‐at‐onset<65) has not been well established and may be key to its understanding and treatment. We utilized in vivo PET imaging to characterize regional patterns of pathological tau accumulation in the Longitudinal Early‐onset Alzheimer’s D...

Background Aβ deposition is thought to start decades prior to symptom onset. Previous studies have shown that mathematical modeling enables reconstruction of Aβ‐PET trajectory and age estimation at Aβ‐PET positivity in Aβ‐positive patients. We aimed to apply this approach to determine Aβ duration and estimate age at Aβ‐PET positivity in sporadic ea...

Background Increased levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 231 (p‐tau231) in plasma have been associated with late‐onset Alzheimer’s Disease (AD). The impact of these biomarkers in early‐onset AD (EOAD) is unclear and the novel plasma biomarker, p‐tau231, has not been studied in this pop...

Background Scalable and accurate diagnostic markers of Alzheimer’s disease and related dementias (ADRD) are urgently needed. A combination of a sensitive brief digital cognitive assessment and plasma biomarkers could represent a promising scalable alternative to standard diagnostic procedures. We evaluated the performance of the TabCAT Brain Health...

Background We examined neuropsychiatric symptoms (NPS) and psychotropic medication use at the midway point of data collection of the Longitudinal Early‐onset Alzheimer’s Disease Study (LEADS). We compared amyloid‐positive early‐onset Alzheimer’s disease (EOAD) participants and amyloid‐negative early‐onset non‐Alzheimer’s disease [EOnonAD]) particip...

Background Patients with a history of repetitive head impacts (RHI) risk progressive memory loss and executive dysfunction consistent with traumatic encephalopathy syndrome (TES). TES is a clinical phenotype sensitive but non‐specific to underlying chronic traumatic encephalopathy (CTE). Cognitive symptoms overlap with Alzheimer’s disease (AD), and...

Background Approximately 10‐25% of amnestic early‐onset dementia are negative for amyloid (Early‐onset non‐Alzheimer’s Disease, EOnonAD). EOnonAD is a heterogenous group with various etiologies. In order to better understand the traits of EOnonAD, we clustered amnestic EOnonAD individuals according to cognitive patterns. Method Cognitive data of 6...

Background The presence of multiple pathologies is the rule and not the exception in Alzheimer’s disease (AD). The goal of this study was to assess whether 18F fluorodeoxyglucose (FDG) PET can provide information about the presence of non‐AD pathologies in autopsy‐proven AD patients. Method Our cohort included 55 patients with antemortem FDG‐PET a...

Background Neurocognitive sequelae of SARS‐CoV‐2 infection have been suggested as potentially leading to a higher incidence of dementia, but the underlying mechanisms remain unclear. By comparing brain magnetic resonance imaging (MRI) between participants with and without a history of SARS‐CoV‐2 infection, prior work identified infection‐related st...

Background Dysfunctional dopamine signaling and disruptions in neurotrophic support are potential exacerbators of Alzheimer’s disease (AD) pathophysiology. A single nucleotide polymorphism (SNP) in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) is associated with greater ventricular expansion and lower scores on the Mini Mental State Exam (M...

Background Alzheimer disease (AD) is defined by the presence of cerebral amyloid‐β plaques and tau neurofibrillary tangles (NFT). Neurophysiological manifestations which depict the functional changes of neurons and circuits, demonstrate that amyloid‐β and tau have distinct effects—high cerebral amyloid‐β burden is associated with increased neural o...

Background Amyloid‐directed therapies will increase the clinical use of amyloid PET. IDEAS captured >17,000 clinical scan interpretations from local radiologists and nuclear medicine physicians. This study aimed to establish accuracy of these interpretations by comparison to expert readers across identical scans. Method Randomly selected amyloid P...

Background Negative AD biomarkers are commonly found in patients with a clinical diagnosis of late‐onset AD, but little is known about biomarker‐negative patients diagnosed with sporadic Early Onset AD (EOAD, <65yo). We explored data from the Longitudinal Early‐onset Alzheimer’s Disease Study (LEADS) to identify such participants and explored amylo...

Background We aimed to determine if burden of cerebral small vessel disease (CSVD) modifies the relationship of plasma amyloid‐beta (Abeta) 42/40 ratio and/or plasma p‐tau 181 with amyloid PET. Method We studied N = 100 participants from the Alzheimer’s Disease Neuroimaging Initiative with 1) Abeta‐42/40 biomarker levels using Quanterix SIMOA (Qua...

Background Posterior cortical atrophy (PCA) is a clinically defined syndrome characterized by impairment in higher‐order visual processing due to neurodegeneration of posterior brain regions (occipito‐parietal and occipito‐temporal areas). Previous findings have reported broader cognitive impairment profiles, but their association with neural corre...

Background Posterior cortical atrophy (PCA) is a neurodegenerative disorder of visuospatial and visuoperceptual impairment with high association to underlying Alzheimer’s disease (AD) pathology. In contrast to typical amnestic AD, risk factors for PCA remain largely unknown. Previously, we observed higher rates of neurodevelopmental differences in...

Background Amyloid‐PET quantification was developed in research settings using highly selected samples, harmonized acquisition protocols, and MRI‐based preprocessing. We aimed to analyze scans from IDEAS, a large‐scale, real‐world study of amyloid‐PET. Major challenges lie in scans being acquired on various PET/PET‐CT/PET‐MR scanners without standa...

Background Flortaucipir F ¹⁸ was the first FDA approved PET tracer to detect tau pathology. Previous studies show that Flortaucipir is more sensitive to Alzheimer’s disease (AD) tau than four‐repeat tauopathies. Furthermore, the neurobiological basis of low Flortaucipir signal remain unclear, especially in basal ganglia. In this study, we aimed to...

Background Increased levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 231 (p‐tau231) in plasma have been associated with late‐onset Alzheimer’s Disease (AD). The impact of these biomarkers in early‐onset AD (EOAD) is unclear and the novel plasma biomarker, p‐tau231, has not been studied in this pop...

Background Flortaucipir F18 was the first FDA approved PET tracer to detect tau pathology. Previous studies show that Flortaucipir is more sensitive to Alzheimer’s disease (AD) tau than four‐repeat tauopathies. Furthermore, the neurobiological basis of low Flortaucipir signal remain unclear, especially in basal ganglia. In this study, we aimed to i...

Background Discordance between the clinical diagnosis of AD by experts after a comprehensive evaluation and AD pathology on autopsy remains common. We sought to identify clinical situations where amyloid‐PET would be most valuable as a diagnostic tool by identifying predictors associated with discordance between initial clinical diagnosis and amylo...

Background The presence of multiple pathologies is the rule and not the exception in Alzheimer’s disease (AD). The goal of this study was to assess whether 18F fluorodeoxyglucose (FDG) PET can provide information about the presence of non‐AD pathologies in autopsy‐proven AD patients. Method Our cohort included 55 patients with antemortem FDG‐PET a...

Background Few prior studies have investigated whether genetic risk for Alzheimer’s disease (AD) can manifest through altered neurodevelopment of AD‐vulnerable brain regions. This pre‐registered study tests the effects of AD polygenic risk on morphometric neurodevelopment across 3 large datasets totaling 8,364 youths aged 3‐22 (Table 1) Method Pol...

Background Dysfunctional dopamine signaling and disruptions in neurotrophic support are potential exacerbators of Alzheimer’s disease (AD) pathophysiology. A single nucleotide polymorphism (SNP) in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) is associated with greater ventricular expansion and lower scores on the Mini Mental State Exam (M...

Background Amyloid‐directed therapies will increase the clinical use of amyloid PET. IDEAS captured >17,000 clinical scan interpretations from local radiologists and nuclear medicine physicians. This study aimed to establish accuracy of these interpretations by comparison to expert readers across identical scans. Method Randomly selected amyloid P...

Background Negative AD biomarkers are commonly found in patients with a clinical diagnosis of late‐onset AD, but little is known about biomarker‐negative patients diagnosed with sporadic Early Onset AD (EOAD, <65yo). We explored data from the Longitudinal Early‐onset Alzheimer’s Disease Study (LEADS) to identify such participants and explored amylo...

Background Aß deposition is thought to start decades prior to symptom onset. Previous studies have shown that mathematical modeling enables reconstruction of Aß‐PET trajectory and age estimation at Aß‐PET positivity in Aß‐positive patients. We aimed to apply this approach to determine Aß duration and estimate age at Aß‐PET positivity in sporadic ea...

Background The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and a hotspot of neurodegenerative processes (e.g., accumulation of tau tangles or TDP‐43). Importantly, the MTL cortex comprises several subregions with distinct functional, cytoarchitectonic, and macro‐anatomical features (Fig. 1). In vivo...