
Jacob Vogel- PhD
- Assistant Professor at Lund University
Jacob Vogel
- PhD
- Assistant Professor at Lund University
About
166
Publications
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Introduction
Current institution
Publications
Publications (166)
In Alzheimer's disease (AD), tau pathology accumulates gradually throughout the brain, with clinical decline reflecting tau progression. A comprehensive understanding of, first, whether tau propagation is predominantly governed by connectome-based diffusion, regional vulnerability, or an interplay of both, and second, which types of brain connectiv...
The distribution of tau pathology in Alzheimer’s disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. We explored whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or...
Alzheimer’s disease (AD) is associated with presymptomatic changes in brain morphometry and accumulation of abnormal tau and amyloid-beta pathology. Studying the development of brain changes prior to symptoms onset may lead to early diagnostic biomarkers and a better understanding of AD pathophysiology. AD pathology is thought to arise from a combi...
Background
Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD), exhibiting spatial heterogeneity across various genetic subgroups, which may be driven by distinct biological mechanisms.
Methods
We employed an integrative imaging transcriptomics approach to identify both disparate and shared transcri...
Background
Substantial variability in tau accumulation patterns in Alzheimer’s disease (AD) population has now become accepted. Subtype and Stage Inference (SuStaIn) has distinguished four distinct spatiotemporal trajectories of tau pathology: limbic (S1), medial temporal lobe‐sparing (S2), posterior (S3), and lateral temporal (S4). A visual method...
Background
Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.
Method
To unco...
Background
With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal a‐synuclein (Lewy body) pathology have become available, complementing pre‐existing tests for Alzheimer’s disease (AD) pathology (Aß an...
Background
Amyloid‐negative tau‐positive PET (A‐T+) participants have been reported in several studies. We assessed the prevalence and characteristics of A‐T+ participants in a cohort of cognitively unimpaired individuals with a first‐degree family history of Alzheimer’s disease (AD) dementia.
Method
We studied 252 participants from the longitudin...
Background
Tau pathology, a hallmark of Alzheimer’s disease (AD), is thought to spread cell‐to‐cell via axonal connections, beginning focally before expanding throughout the brain. This study uses computational models to investigate the interplay between network spread and regional vulnerability in influencing tau spread, focusing specifically on M...
Background
With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal α‐synuclein (Lewy body) pathology have become available, complementing pre‐existing tests for Alzheimer’s disease (AD) pathology (Aβ an...
Background
Several studies have recently emerged describing relationships between cerebrospinal fluid (CSF) proteins and beta‐amyloid (Aβ) and tau pathology. While these studies have primarily characterized Alzheimer’s disease (AD) proteinopathies using CSF markers, positron emission tomography (PET) more accurately captures these pathologies, espe...
Background
Amyloid‐negative tau‐positive PET (A‐T+) participants have been reported in several studies. We assessed the prevalence and characteristics of A‐T+ participants in a cohort of cognitively unimpaired individuals with a first‐degree family history of Alzheimer’s disease (AD) dementia.
Method
We studied 252 participants from the longitudin...
Background
Substantial variability in tau accumulation patterns in Alzheimer’s disease (AD) population has now become accepted. Subtype and Stage Inference (SuStaIn) has distinguished four distinct spatiotemporal trajectories of tau pathology: limbic (S1), medial temporal lobe‐sparing (S2), posterior (S3), and lateral temporal (S4). A visual method...
Background
Fluid biomarkers represent an informative and cost‐effective way to detect and monitor Alzheimer’s disease (AD). However, as we recently showed, the overall proteome average in CSF exhibits a non‐disease related average signal (inter‐individual variability), which can reduce the precision of concentration based CSF AD biomarkers.¹ Now, w...
Background
A generative model of tau PET was applied to multiple cohorts across the Alzheimer's disease (AD) spectrum, revealing longitudinal changes in tau production and transport. A generalisation of the model accounts for amyloid, tau and neurodegeneration (ATN) interactions and accurately explains longitudinal ATN biomarker data, adding potent...
Background
A key characteristic of Alzheimer’s disease (AD) is cerebral aggregation of tau. These aggregates can be quantified and localized with positron emission tomography (PET), which improves the diagnostic and prognostic work‐up of AD. However, tau‐PET is expensive and not available in clinical settings globally. With emerging disease‐modifyi...
Background
Cerebrospinal fluid (CSF) proteomics allows for characterization of multiple disease‐related biological processes in vivo . These processes likely occur along temporal cascades mirroring disease evolution. This study describes interindividual variation in these cascades, in the context of Alzheimer’s disease.
Method
Participants were re...
Background
Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.
Method
To unco...
Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well a...
Hemispheric asymmetry is a universal property of brain organization with wide implications into brain function and structure, and diseases. This study presents a laterality index for characterizing hemispheric asymmetries that underlie cortical maps using geometric eigenmodes derived from human cortical surfaces. We develop a generalized design to...
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by the aggregation of β-amyloid (Aβ) and tau in the brain. Breakthroughs in disease-modifying treatments targeting Aβ bring new hope for the management of AD. But to effectively modify and someday even prevent AD, a better understanding is needed of the biolo...
Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer’s disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differe...
Cortical atrophy in behavioral variant frontotemporal degeneration (bvFTD) exhibits spatial heterogeneity across genetic subgroups, potentially driven by distinct biological mechanisms. Using an integrative imaging-transcriptomics approach, we identified disparate and shared transcriptomic signatures associated with cortical thickness in C9orf72, G...
Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathol...
Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human br...
The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 livin...
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...
Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-...
Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.
To uncover distinct atrop...
Biological staging of individuals with Alzheimer’s disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers....
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...
Background: Excess weight in adulthood leads to health complications such as diabetes, hypertension, or dyslipidemia. Recently, excess weight has also been related to brain atrophy and cognitive decline. Reports show that obesity is linked with Alzheimer’s disease (AD)-related changes, such as cerebrovascular damage or amyloid-β accumulation. Howev...
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
Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD). Distinct atrophy patterns across different form of genetic bvFTD may be shaped by their different underlying biology. This study aimed to use an integrative imaging transcriptomics approach to identify shared and disparate transcriptomic...
Background
Cerebral small vessel disease (SVD) is a cerebrovascular condition associated with age that contributes to dementia, stroke, and other neurological disorders. White matter lesions (WML), microbleeds, and infarcts are hallmarks of SVD, but their molecular mechanisms are poorly understood. The aim of this study was to investigate the CSF p...
Background
a‐synuclein aggregation is a pathologic hallmark of several Lewy body disorders with differing symptoms. This symptom heterogeneity may be due to varying underlying disease trajectories. Here, we use a data‐driven approach to identify and characterize distinct spatial‐temporal progression patterns of α‐synuclein deposition.
Method
The S...
Background
Staging Alzheimer’s disease (AD) allows for the identification of key milestones and inflection points in the disease course. However, most current in vivo disease staging methods rely on costly and low‐accessible measures such as PET. Our objective was to generate and evaluate a staging model based on multiple cerebrospinal fluid (CSF)...
Background
A growing number of resting‐state fMRI (rs‐fMRI) studies report changes in network activity to be a frequent and often early pathological feature in many neurodegenerative conditions. The majority of studies have primarily focused on changes in group averages, failing to account for individual functional connectivity (FC) idiosyncrasies...
Background
To better understand the pathophysiological processes in Alzheimer’s disease (AD), we need to broaden our knowledge on molecular pathways and discover molecular markers that co‐occur with, precipitate and follow the accumulation beta‐amyloid (Aβ) and tau pathology. Using high‐throughput proteomics, we investigated how a wide array of pro...
Background
a‐synuclein aggregation is a pathologic hallmark of several Lewy body disorders with differing symptoms. This symptom heterogeneity may be due to varying underlying disease trajectories. Here, we use a data‐driven approach to identify and characterize distinct spatial‐temporal progression patterns of a‐synuclein deposition.
Method
The S...
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
Staging Alzheimer’s disease (AD) allows for the identification of key milestones and inflection points in the disease course. However, most current in vivo disease staging methods rely on costly and low‐accessible measures such as PET. Our objective was to generate and evaluate a staging model based on multiple cerebrospinal fluid (CSF)...
Lewy body (LB) disorders, characterized by the aggregation of misfolded alpha-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. By applying data-driven disease progression modelling to regional neuropathological LB density scores from 814 brain donors, we describ...
Background
TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS–FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to...
Human brain size changes dynamically through early development, peaks in adolescence, and varies up to 2-fold among adults. However, the molecular genetic underpinnings of interindividual variation in brain size remain unknown. Here, we leveraged postmortem brain RNA sequencing and measurements of brain weight (BW) in 2,531 individuals across three...
White matter hyperintensities (WMHs) are radiological abnormalities reflecting cerebrovascular dysfunction detectable using magnetic resonance imaging (MRI). WMHs are often present in individuals at the later stages of the lifespan and in prodromal stages in the Alzheimer’s Disease spectrum. Tissue alterations underlying WMHs may include demyelinat...
Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimer’s disease, and its accumulation exhibits a rich spatio-temporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatio-temporal process is orchestrated – namely, to w...
Neurodegenerative diseases are the most common cause of dementia. Although their underlying molecular pathologies have been identified, there is substantial heterogeneity in the patterns of progressive brain alterations across and within these diseases. Recent advances in neuroimaging methods have revealed that pathological proteins accumulate alon...
Neuroimaging is commonly used to infer human brain connectivity, but those measurements are far-removed from the molecular underpinnings at synapses. To uncover the molecular basis of human brain connectivity, we analyzed a unique cohort of 98 individuals who provided neuroimaging and genetic data contemporaneous with dendritic spine morphometric,...
Background
TDP-43 proteinopathies represents a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study aimed to us...
Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic work-up of dementia in clinical practice and the design of clinical trials. Here, we created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm by evaluating cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau biomarkers in 426...
Amyloid-β is thought to facilitate the spread of tau throughout the neocortex in Alzheimer's disease, though how this occurs is not well understood. This is because of the spatial discordance between amyloid-β, which accumulates in the neocortex, and tau, which accumulates in the medial temporal lobe during ageing. There is evidence that in some ca...
Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related mechanisms which vary between individuals, such a...
Importance:
Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to conventional approaches where the same ROI (group-...
TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterise TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use...
Hierarchical processing requires activity propagating between higher- and lower-order cortical areas. However, functional neuroimaging studies have chiefly quantified fluctuations within regions over time rather than propagations occurring over space. Here, we leverage advances in neuroimaging and computer vision to track cortical activity propagat...
Pathological aggregation of tar DNA‐binding protein 43 (TDP‐43) in the brain is the primary cause of many cases of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and limbic‐predominant age‐related TDP‐43 encephalopathy (LATE). It is therefore imperative to establish empirical staging systems to characterize and distin...
Longitudinal tau‐PET is increasingly used as an outcome in clinical trials evaluating disease‐modifying therapies in Alzheimer’s disease (AD). In order to quantify change in tau‐PET signal over time, regions of interest (ROIs) are used; to date, these have been based on neuropathological studies or data‐driven approaches where the same ROI is used...
Evidence from previous PET imaging studies suggests that increased neocortical tau seen in APOE‐ε4 carriers can be explained by the higher levels of neocortical amyloid‐β (Aβ) pathology also seen in this group. However, these studies also suggest an amyloid‐independent association between APOE‐ε4 and medial temporal lobe (MTL) tau. Using neuropatho...
Tau pathology is a hallmark of Alzheimer’s disease, but measuring this pathology in vivo with PET is expensive. MRI represents a low‐cost alternative for measuring in vivo disease progression, but is non‐specific. We present an MR‐based marker of tau‐specific pathology using machine learning (ML). 1851 pairs of RO948 tau‐PET and T1‐weighted MRI sca...
Tau pathology is a hallmark of Alzheimer’s disease, but measuring this pathology in vivo with PET is expensive. MRI represents a low‐cost alternative for measuring in vivo disease progression, but is non‐specific. We present an MR‐based marker of tau‐specific pathology using machine learning (ML). 1851 pairs of RO948 tau‐PET and T1‐weighted MRI sca...
Background
Excess weight in adulthood leads to health complications such as diabetes, hypertension, or dyslipidemia. Recently, excess weight has also been related to brain atrophy and cognitive decline. Reports show that obesity is linked with Alzheimer’s disease (AD)-related changes, such as cerebrovascular damage or amyloid-β accumulation. Howeve...
Several studies have shown decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD). However, the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, PET, and CSF biomarkers, we investigated the associations between gray matter (GM)-CBF and the key mechanisms in AD including amyloid-β (Aβ)...
Human brain size increases dynamically through early development, peaks in adolescence, and varies up to two-fold among adults. Although previous studies have elucidated changes in brain size across evolution, development, traits, and diseases, the molecular underpinnings of interindividual variation in brain size remain unknown. Here, we leverage...
Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, how these gradients relate to adult brain function, and whether they are maintained in the adult brain, remains unknown. Here we uncover three axes of topographic variati...
The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions...
Importance:
Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET).
Objective:
To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease.
Design, setting, and particip...
Prior work has shown that there is substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, or functional topography. However, it remains unknown whether there are sex differences in the topography of individualized networks in youth. Here, we leveraged an advanced machine learning method...
Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...
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
Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage t...
Hierarchical processing requires activity propagating between higher and lower-order cortical areas. However, studies of brain development have chiefly quantified fluctuations within regions over time rather than propagations occurring over space. Here, we leveraged advances in neuroimaging and computer vision to track cortical activity propagation...
The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions...
BACKGROUND
The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth.
METHODS
T...
Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight ¹ . Here we assemble an...
Background: Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage...
The distribution of Alzheimer’s disease (AD) tau pathology varies systematically and causes a diverse array of syndromes. This forum article provides a brief overview of key controversies in untangling the complexity of AD subtypes, explores potential causes of AD variability in the population, and discusses clinical relevance and future directions...
Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...
Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...
Accurate prediction of progression in subjects at risk of Alzheimer's disease is crucial for enrolling the right subjects in clinical trials. However, a prospective comparison of state-of-the-art algorithms for predicting disease onset and progression is currently lacking. We present the findings of "The Alzheimer's Disease Prediction Of Longitudin...
Importance
There is currently no consensus as to which biomarkers best predict longitudinal tau accumulation at different clinical stages of Alzheimer disease (AD).
Objective
To describe longitudinal [¹⁸F]RO948 tau positron emission tomography (PET) findings across the clinical continuum of AD and determine which biomarker combinations showed the...
Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI).
Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB)...
Background
A large body of evidence has shown decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD). However, the link between CBF and the primary AD pathologies as well as synaptic integrity remains unclear.
Method
Baseline CBF was measured using arterial spin labeling (ASL) in a 3T MRI scanner in 137 cognitively unimpaired individuals...
Background
In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau‐PET imaging to investigate the sequence of tau pathology progres...
Regulation of gene expression drives protein interactions that govern synaptic wiring and neuronal activity. The resulting coordinated activity among neuronal populations supports complex psychological processes, yet how gene expression shapes cognition and emotion remains unknown. Here, we directly bridge the microscale and macroscale by mapping g...
The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex that has been implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. Capital...
Subtype and Stage Inference (SuStaIn) is an unsupervised learning algorithm that uniquely enables the identification of subgroups of individuals with distinct pseudo-temporal disease progression patterns from cross-sectional datasets. SuStaIn has been used to identify data-driven subgroups and perform patient stratification in neurodegenerative dis...
Although several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, positron emission tomography, and biomarkers of cerebrospinal fluid, we investigated the associations between CBF and the key mechanisms in...
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 AD subtypes have b...
Over the past 25 years, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, there are no reference standards against which to anchor measures of individual differences in brain morphology, in contrast to growth charts for traits such as height and weight. Here, we built an interactive online...
Prior work has shown that there is substantial interindividual variation in the spatial distribution of functional networks across the cerebral cortex, or functional topography . However, it remains unknown whether there are sex differences in the topography of individualized networks in youth. Here we leveraged an advanced machine learning method...
Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we ident...