A5081751572- Functional Brain Connectivity Studies
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Advanced Neuroimaging Techniques and Applications
- Neural dynamics and brain function
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Bone and Joint Diseases
- EEG and Brain-Computer Interfaces
- Medical Imaging Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- Glioma Diagnosis and Treatment
- Mental Health Research Topics
- MRI in cancer diagnosis
- Peroxisome Proliferator-Activated Receptors
- Inflammation biomarkers and pathways
- Memory Processes and Influences
- Epilepsy research and treatment
- Cognitive Functions and Memory
- Neurobiology of Language and Bilingualism
- Memory and Neural Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Autism Spectrum Disorder Research
- Neurogenesis and neuroplasticity mechanisms
- Advanced MRI Techniques and Applications
Ludwig-Maximilians-Universität München
2021-2025
LMU Klinikum
2021-2025
University of Lübeck
2017-2021
Institut d'Investigació Biomédica de Bellvitge
2017
La Trobe University
2017
Abstract For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade Aβ- tau-related processes. Therefore, set out investigate how Aβ soluble phosphorylated tau (p-tau) relate accumulation aggregates assessed with PET subsequent cognitive decline across Alzheimer’s disease (AD) continuum. Using human cross-sectional longitudinal neuroimaging assessment data, show that in early stages AD, increased concentration CSF p-tau...
Abstract Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. assumed to spread prion-like across connected neurons, but mechanisms tau propagation are largely elusive characterized not only by also astroglial oligodendroglial accumulation. Here, we assess whether connectivity associated with 4R-tau deposition patterns combining resting-state fMRI connectomics both 2 nd generation 18...
Abstract In Alzheimer’s disease, amyloid-beta (Aβ) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote spreading. Aβ induces activity, manifesting in increases presynaptic growth-associated protein 43 (GAP-43), which is closely involved plasticity. We therefore tested whether Aβ-related GAP-43 increases, as a marker changes, drive spreading 93 patients across aging spectrum with available CSF GAP-43, amyloid-PET longitudinal tau-PET...
In Alzheimer’s disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration cognitive decline. However, pathophysiological link between Aβ remains unclear, hinders therapeutic efforts to attenuate Aβ-related accumulation. has been found trigger neuronal hyperactivity hyperconnectivity, preclinical research shown that spreads across connected neurons in an activity-dependent manner. Here, we hypothesized hypersynchronicity, resulting...
To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers future cognitive decline in older adults with without impairment.In this longitudinal study, we included 396 cognitively normal to dementia subjects 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET ~ 2-year follow-up. Annual change rates global cognition (i.e., MMSE, ADAS13) episodic memory were calculated via linear-mixed models. We determined amyloid-PET (Centiloid) plus...
Abstract In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated progression and tau spreading, yet the mechanisms underlying faster manifestation are unknown. To address this, we combined resting-state fMRI longitudinal tau-PET in two independent samples of controls biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, found that symptomatic showed stronger globally connected fronto-parietal hubs, i.e., regions critical for...
For the Alzheimer disease (AD) therapies to effectively attenuate clinical progression, it may be critical intervene before onset of amyloid-associated tau spreading, which drives neurodegeneration and cognitive decline. Time points at spreading accelerates depend on individual risk factors, such as apolipoprotein E ε4 (ApoE4) carriership, is linked faster progression; however, association ApoE4 with amyloid-related unclear.
Report9 January 2023Open Access Source DataTransparent process sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease Davina Biel orcid.org/0000-0002-2597-1992 Institute for Stroke Dementia Research (ISD), University Hospital, LMU Munich, Germany Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Writing - original draft, review & editing Search more papers by this author Marc Suárez-Calvet...
Abstract Alzheimer’s disease and cerebral small vessel are the two leading causes of cognitive decline dementia coexist in most memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature both disease. However, disease-specific biomarkers white alterations missing. Recent advances operating on fixel level (fibre population within voxel) promise to advance our understanding disease-related alterations. Fixel-based analysis allows derivation measures...
Learning the associations between words and meanings is a fundamental human ability. Although language network cortically well defined, role of white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual cross-situational word learning, we tested whether learning meaning new related to integrity language-related in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital inferior-longitudinal fasciculi were virtually dissected...
Aggregated alpha-Synuclein (αSyn) is a hallmark pathology in Parkinson's disease but also one of the most common co-pathologies Alzheimer's (AD). Preclinical studies suggest that αSyn can exacerbate tau aggregation, implying co-pathology may specifically contribute to Aβ-induced aggregation drives neurodegeneration and cognitive decline AD. To investigate this, we combined novel CSF-based seed-amplification assay (SAA) determine positivity with amyloid- tau-PET neuroimaging large cohort...
Abstract Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer’s disease, and the heterogeneity of tau-PET patterns matches symptom heterogeneity. Thus, may allow precision-medicine prediction individual tau-related trajectories, which can be important determining patient-specific endpoints clinical trials. Here, we aimed to examine whether cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows domain-specific decline. Further, determine...
Abstract Introduction Lower network segregation is associated with accelerated cognitive decline in Alzheimer's disease (AD), yet it unclear whether less segregated brain networks facilitate connectivity‐mediated tau spreading. Methods We combined resting state functional magnetic resonance imaging (fMRI) longitudinal positron emission tomography (PET) 42 betamyloid‐negative controls and 81 amyloid beta positive individuals across the AD spectrum. Network was determined using resting‐state...
Abstract Age-related cognitive decline has been linked to alterations of the dopaminergic system and its subcortical trajectories. Recent work suggests a critical role iron accumulation within basal ganglia (BG) in verbal memory performance, increased levels have related demyelination. However, specificity age-related increases with respect functions remains unclear. Therefore, we investigated interplay age, structural integrity BG. In total, 79 healthy older participants underwent broad...
In humans, exposure to novel images and exploration of virtual environments before the encoding words improved subsequent memory performance. Animal studies revealed similar effects novelty, both after learning, could show that hippocampus-dependent dopaminergic neuromodulation plays an important role. Here, we further investigated novelty on long-term in humans using a paradigm employing short sequences nature movies presented either or at two time points learning unrelated words. Since...
Abstract Cognitive training should not only improve performance of the trained task, but also untrained abilities. Exposure to novelty can subsequent memory performance, suggesting that exposure might be a critical factor promote effects cognitive training. Therefore, we combined 4‐week working with exposure. Neuropsychological tests and MRI data were acquired before after analyze behavior changes in gray matter volume, myelination, iron levels. In total, 83 healthy older humans participated...
ABSTRACT For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ soluble phosphorylated tau (p-tau) relate the accumulation aggregates assessed with PET subsequent cognitive decline across Alzheimer’s disease (AD) continuum. In early stages AD, increased concentration CSF p-tau was main driver insoluble brain, mediated effect on aggregation. Further, higher concentrations were mainly related faster in regions strong functional connectivity...
ABSTRACT INTRODUCTION Tau pathology in Alzheimer’s disease tracks clinical status more closely than beta-amyloid. Thus, tau-PET may be a promising prognostic marker for cognitive decline. Here, we systematically compared and Braak-staging vs. amyloid-PET as predictors of METHODS We included 396 cognitively normal to dementia subjects with 18 F-Flutemetamol/ F-Florbetapir-amyloid-PET, F-Flortaucipir-tau-PET ~2-year assessments. Annual change rates were calculated via linear-mixed models....
Abstract Background Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4‐repeat (4R) tauopathies its role accelerating disease progression. Objective We tested whether microglial activation (1) progresses similar spatial patterns the pathology tau spreads across interconnected brain regions, (2) degree of parallels spreading. Methods examined vivo associations between aggregation 31...
Abstract Background In Alzheimer’s disease, Aβ triggers tau spreading which drives neurodegeneration and cognitive decline. However, the mechanistic link between remains unclear, hinders therapeutic efforts to attenuate Aβ‐related accumulation. Preclinical research could show that spreads across connected neurons in an activity‐dependent manner, was shown trigger neuronal hyperactivity hyperconnectivity. Therefore, we hypothesized induces hyperconnectivity, thereby promoting from initial...
Abstract Background Understanding modulators of Alzheimer's disease’s (AD) progression is crucial for determining optimal treatment windows and targets. Apolipoprotein E ε4 (ApoE4), i.e. a key AD risk factor, associated with earlier tau accumulation at lower Aβ levels (Steward et al. 2023), yet, the mechanisms driving this connection remain unclear. Thus, we assessed whether ApoE4 accelerates initial Aβ‐related secretion measurable in CSF or subsequent aggregation as determined via PET...
Abstract Background Memory clinic patients typically present with Alzheimer’s disease (AD) and cerebral small vessel (SVD) to varying degrees. Therefore, it is crucial determine the etiology of cognitive deficits for facilitating patient‐centered treatment in memory clinics. Plasma biomarkers (ptau 217 , Glial Fibrillary Acidic Protein [GFAP], Neurofilament light chain [NfL]) fixel‐based advanced diffusion MRI markers (fiber density, fiber‐bundle cross‐section) show potential towards...