Brian Andrew Gordon

Brian Andrew Gordon
Washington University in St. Louis | WUSTL , Wash U · Department of Radiology

PhD

About

292
Publications
44,026
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Introduction
I am an Assistant Professor in the Department of Radiology at the Washington University in St. Louis School of Medicine. In addition I am a faculty member of the Hope Center for Neurological Disorders and a member of the Knight Alzheimer's Disease Research Center. My research studies healthy aging and Alzheimer's disease. My current focus is primarily on changes occurring in preclinical phases of both sporadic and autosomal dominant Alzheimer's disease. This work integrates multiple neuroimaging techniques (PET, structural MRI, and functional MRI) alongside biofluid assays (CSF and blood) and behavioral testing.
Additional affiliations
September 2014 - July 2016
Washington University in St. Louis
Position
  • Research Faculty
August 2010 - September 2013
Washington University in St. Louis
Position
  • PostDoc Position
August 2003 - August 2010
University of Illinois, Urbana-Champaign
Position
  • PhD Student

Publications

Publications (292)
Article
Full-text available
View largeDownload slide Tau pathology is a hallmark of Alzheimer’s disease but until recently could only be measured in cerebrospinal fluid. Using PET, Gordon et al. demonstrate elevated tau deposition in medial temporal, parietal, and medial prefrontal cortex in individuals with dementia. PET tracer uptake strongly correlates with tauopathy meas...
Article
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Alzheimer's disease (AD) is characterized by two molecular pathologies: cerebral b-Amyloidosis in the form of b-Amyloid (Ab) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Ab could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau...
Article
Full-text available
Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are corr...
Article
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Objective: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Methods: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate...
Article
Introduction: As Alzheimer's disease (AD) biomarkers rapidly develop, tools are needed that accurately and effectively communicate risk of AD dementia. Methods: We analyzed longitudinal data from >10,000 cognitively unimpaired older adults. Five-year risk of AD dementia was modeled using survival analysis. Results: A demographic model was deve...
Article
Objective Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer’s disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing s...
Preprint
Full-text available
Background Estimates of “brain-predicted age” quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD), but has not been well explored in preclinical AD. Prior studies have typically modeled BAG with stru...
Article
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Rationale: Off-target binding of 18F-flortaucipir (FTP) can complicate quantitative positron emission tomography (PET) analyses. An underdiscussed off-target region is the skull. Here we characterize how often FTP skull binding occurs, its influence on estimates of Alzheimer disease (AD) pathology, its potential drivers, and whether skull uptake is...
Article
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...
Article
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Alzheimer’s disease biomarkers are widely accepted as surrogate markers of underlying neuropathological changes. However, few studies have evaluated whether preclinical Alzheimer’s disease biomarkers predict Alzheimer’s neuropathology at autopsy. We sought to determine whether amyloid PET imaging or CSF biomarkers accurately predict cognitive outco...
Article
Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicate...
Preprint
Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal...
Article
The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of ‘sporadic’ late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI...
Preprint
Importance National Institute on Aging-Alzheimer’s Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer’s disease (AD). Objective Assess the clinical value of these biological criteria for prediction of near-term cognitive impairment in cognitively unimpaired older i...
Article
Full-text available
Objective: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231) and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups. Methods: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to sel...
Article
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Amyloid-beta (Aβ) deposition is one of the hallmark pathologies in both sporadic Alzheimer’s disease (sAD) and autosomal dominant Alzheimer’s disease (ADAD), the latter of which is caused by mutations in genes involved in Aβ processing. Despite Aβ deposition being a centerpiece to both sAD and ADAD, some differences between these Alzheimer’s diseas...
Article
Full-text available
Background Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disea...
Article
Introduction: As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others. Methods: We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal...
Article
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Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain...
Article
Full-text available
“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC...
Preprint
The Dominantly Inherited Alzheimer Network (DIAN) Observational Study is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). This rare form of Alzheimer disease (AD) is caused by mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. As individuals from these families...
Article
Background Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s). Methods In autosomal dominant AD (ADAD) mutation carriers (MC)...
Article
Background Insights gained from studying individuals with autosomal dominant Alzheimer's disease have broadly influenced mechanistic hypotheses, biomarker development, and clinical trials in both sporadic and dominantly inherited Alzheimer's disease. Although pathogenic variants causing autosomal dominant Alzheimer's disease are highly penetrant, t...
Article
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Background Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer's disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongl...
Preprint
Background: Heterogeneity in progression to AD poses challenges for both clinical prognosis and clinical trial implementation. In the absence of a well-defined understanding of future disease trajectory, participants may receive unnecessary treatment or true effects of pharmacological intervention may be obscured. We identified early differences in...
Article
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Although often unmeasured in studies of cognition, many older adults possess Alzheimer disease (AD) pathologies such as beta-amyloid (Aβ) deposition, despite being asymptomatic. We were interested in examining whether the behavior-structure relationship observed in later life was altered by the presence of preclinical AD pathology. 511 cognitively...
Preprint
Full-text available
Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and wo...
Article
Full-text available
Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of A...
Article
In addition to anti‐Aβ immunization therapeutics completing phase II/III clinical trials1, drugs targeting tau, inflammation, and apolipoprotein E, are in clinical development. Due to its close association with cognitive and clinical impairment, tau is one of the most promising targets currently ready for phase II trials. In this study, using the l...
Article
Traditional plate‐based assays for cerebrospinal fluid (CSF) biomarkers have been limited by relatively high assay variance that reduces the accuracy of individual measurements. Next generation automated assay platforms for CSF biomarkers reduce the variability of measurements, including across sample runs. In the current study, we utilized the Lum...
Conference Paper
Amyloid‐related imaging abnormalities (ARIA), edema (E) or hemorrhagic (H) type, have been reported in trials of anti‐β‐amyloid passive immunotherapies in sporadic and dominantly inherited Alzheimer Disease (DIAD). However, beyond APOE‐ɛ4 the risk factors and clinical implications of ARIA are not well understood, especially in DIAD populations. Her...
Article
Recent advances in the development of novel Alzheimer’s disease (AD) measures of amyloid, tau, and neurodegeneration in cerebrospinal fluid (CSF) and blood have enabled a better understanding of the links between amyloid‐beta (Aβ), tau species and neurodegeneration in the brain, CSF, and blood. The discoveries of novel tau species in CSF and blood,...
Article
Approximately 5% of Alzheimer disease (AD) occurs before the age of 65, known as early onset AD (EOAD); 5‐10% of the patients with EOAD are caused by dominantly inherited mutations (DIAD) and the remainder appear to be sporadic EOAD (sEOAD). The extent to which clinical presentations, cognitive and biomarker profiles in DIAD and sEOAD overlap remai...
Article
Numerous biomarkers exist for potentially studying autosomal dominant Alzheimer disease (ADAD) pathology. Understanding the relationships between biomarkers and disease progression can inform patient care and clinical trials. We utilized machine learning‐based clustering and feature selection to identify an optimal subset of biomarkers reflective o...
Conference Paper
Results from the first Dominantly Inherited Alzheimer Network Trials Unit (DIAN‐TU) clinical trial showed Gantenerumab reduces amyloid‐β deposition in autosomal dominant Alzheimer disease individuals. However, it is uncertain whether these initial findings from [11C]PiB PET generalize to other amyloid‐β PET radiotracers. We acquired [11C]PiB and [1...
Article
Brain atrophy has been shown to occur with age, but it is unclear if this is misattribution of undetected preclinical Alzheimer disease (AD). Here we determine regional patterns of age‐related atrophy in a cross‐sectional cohort screened for the confounding influence of preclinical Alzheimer disease. We assembled two dementia‐free cohorts ‐ a Norma...
Article
Background: A small proportion of Alzheimer disease (AD), known as early onset AD (EOAD), has symptomatic age at onset (AAO) before age 65. About 5-10% of EOAD is dominantly inherited (DIAD); the rest is termed to be sporadic (sEOAD). Although DIAD and sEOAD share the hallmark plaques and tangles that define AD neuropathologic change (ADNC), the r...
Article
Previous research has shown that with age and disease, the integrity of grey matter structures decline. One such measure of grey matter integrity is cortical thickness, where lower values represent thinning of the cortical surface. Given that cognitive performance tends to decline with age, we were interested in investigating whether performance on...
Article
The apolipoprotein E (APOE) ε4 allele is the most well‐established genetic risk factor for late‐onset Alzheimer disease (AD). The ε4 allele is strongly linked with cerebral β‐amyloidosis whereas its relationship with tauopathy is less established. Here we investigate the relationship between APOE ε4 carrier status, regional amyloid‐β‐ (Aβ) and tau‐...
Article
Mutations in the Presenilin‐1 (PS1) gene account for 80% of dominantly inherited Alzheimer disease (DIAD). Previous findings suggest PS1 mutation position relative to codon 200 may impact the distribution and amount of cerebral β‐amyloid pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of mutation position on imaging mar...
Article
Approximately 5% of patients with Alzheimer’s Disease (AD) develop symptoms before age 65, with this early‐onset presentation attributed to either sporadic (sEOAD) or dominantly‐inherited (DIAD) etiology. Both sEOAD and DIAD are characterized by brain amyloid‐beta (Aβ) accumulation and neurodegeneration, but differences in topography and magnitude...
Article
Though pathogenic variations in PSEN1 leading to Autosomal Dominant Alzheimer's disease (ADAD) are all highly penetrant, there is substantial inter‐individual variability in the rates of cognitive decline and biomarker change observed in ADAD. We hypothesized that this inter‐individual variability may be associated with the location of the pathogen...
Article
Full-text available
Pittsburgh compound B (PiB) radiotracer for positron emission tomography (PET) imaging can bind to different types of amyloid-β plaques and blood vessels (cerebral amyloid angiopathy). However, the relative contributions of different plaque subtypes (diffuse versus cored/compact) to in vivo PiB PET signal on a region-by-region basis are incompletel...
Article
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Background Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a “sampling” of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and admi...
Article
Objective To predict when cognitively normal individuals with brain amyloidosis will develop symptoms of Alzheimer disease (AD). Methods Brain amyloid burden was measured by amyloid PET with Pittsburgh compound B. The mean cortical standardized uptake value ratio (SUVR) was transformed into a timescale using longitudinal data. Results Amyloid acc...
Article
Brain atrophy occurs in aging even in the absence of dementia, but it is unclear to what extent this is due to undetected preclinical Alzheimer disease. Here we examine a cross-sectional cohort (ages 18-88) free from confounding influence of preclinical Alzheimer disease, as determined by amyloid PET scans and three years of clinical evaluation pos...
Preprint
Full-text available
Therapeutic modulation of TREM2-dependent microglial function provides an additional strategy to slow progression of Alzheimer disease (AD). Although studies on animal models suggest that TREM2 is protective, the trigger of increased TREM2 expression during disease progression and its clinical and pathological consequences in AD remain unclear. We...
Article
Full-text available
Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We cr...
Article
Neurodegenerative disease is highly prevalent among older adults and, if undetected, may obscure estimates of cognitive change among aging samples. Our aim in this study was to determine the nature and magnitude of cognitive change in the absence of common neuropathologic markers of neurodegenerative disease. Cognitively normal older adults (ages 6...
Article
Objective: Temporal correlations between CSF and neuroimaging (PET and MRI) measures of amyloid, tau, and neurodegeneration were evaluated in relation to Alzheimer disease (AD) progression. Methods: Three hundred seventy-one cognitively unimpaired and impaired participants enrolled in longitudinal studies of AD had both CSF (amyloid-β42, phospho...
Article
Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a f...
Presentation
Presentation discussing the region-specific effects of Gantenerumab use on neuroimaging biomarkers in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU)
Article
Full-text available
In Alzheimer’s disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNFVal66Met an important modulating factor of cognitive impairment in AD. However, the e...
Article
Full-text available
Objective To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluated longitudinally families affected by dominantly inherited Alzheimer diseas...
Article
Introduction: Machine learning models were used to discover novel disease trajectories for autosomal dominant Alzheimer's disease. Methods: Longitudinal structural magnetic resonance imaging, amyloid positron emission tomography (PET), and fluorodeoxyglucose PET were acquired in 131 mutation carriers and 74 non-carriers from the Dominantly Inher...
Article
Full-text available
Aim: Identify a global resting state functional connectivity (gFC) signature in mutation carriers (MC) from the Dominantly Inherited Alzheimer Network (DIAN). Assess the gFC with regards to amyloid (A), tau (T), and neurodegeneration (N) biomarkers and estimated years to symptom onset (EYO). Introduction: Cross-sectional measures were assessed i...
Article
Full-text available
The contributors to persistent cognitive impairment and hippocampal atrophy in leucine-rich glioma-inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [ 18 F]flor-taucipir PET neuroimaging associated with persistent cognitive impairment and hippocampal atrophy in four recovering LGI...
Article
Background and purpose The factors that predispose to relapse in patients recovering with autoimmune encephalitis (AE) are largely unknown, complicating efforts to distinguish patients with resurgent symptoms who may benefit from additional immune-modulating therapies from those with other causes of impairment. Methods We report a patient with AE...
Article
Full-text available
Personality traits such as Neuroticism and Conscientiousness are associated with Alzheimer disease (AD) pathophysiology in cognitively normal (CN) and impaired individuals, and may represent potential risk or resilience factors, respectively. This study examined the cross-sectional relationship between personality traits and regional tau deposition...
Article
Full-text available
Gantenerumab is a humanized anti‐amyloid‐beta monoclonal antibody in clinical development for the treatment of several stages of Alzheimer disease (AD). Gantenerumab was evaluated in a phase 2/3 clinical trial program designed to evaluate its efficacy in autosomal dominant AD based on a combination of clinical and biomarker evidence. The study enro...
Conference Paper
The grey matter covariance network of the brain, extracted from structural MR, becomes disrupted in neurodegenerative disorders such as Alzheimer disease (AD). While these disruptions ‐ as indicated by lower small‐world values ‐ relate to cognitive performance and can predict subsequent cognitive decline, the precise biological underpinnings of the...
Article
During aging, brain networks become less functionally specialized, known as dedifferentiation. When dedifferentiation occurs, brain networks become less adaptive, leading to failures in cognitive processing. Although global dedifferentiation occurs with age, it is unknown how global and local dedifferentiation change as a function of cognitive impa...