A5063922280- Dementia and Cognitive Impairment Research
- Functional Brain Connectivity Studies
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Epilepsy research and treatment
- Prion Diseases and Protein Misfolding
- Folate and B Vitamins Research
- Spatial Cognition and Navigation
- Neurological Disease Mechanisms and Treatments
- Color perception and design
- Visual perception and processing mechanisms
- Neurological Disorders and Treatments
German Center for Neurodegenerative Diseases
2018-2022
University of Wisconsin–Madison
2021
University of Rostock
2019
Amyloid deposition and neurofibrillary degeneration in Alzheimer's disease specifically affect discrete neuronal systems, but the underlying mechanisms that render some brain regions more vulnerable to pathology than others remain largely unknown. Here we studied molecular properties these distinct regional vulnerabilities by analysing disease-typical neuroimaging patterns of amyloid neurodegeneration relation gene expression profiles human brain. Graded brain-wide vulnerability were...
Abstract Positron emission tomography (PET)‐based staging of regional amyloid deposition has recently emerged as a promising tool for sensitive detection and stratification pathology progression in Alzheimer's Disease (AD). Here we present an updated methodological framework PET‐based using region–specific amyloid‐positivity thresholds assess its longitudinal validity serial PET acquisitions. We defined region‐specific based on Florbetapir‐PET data 13 young healthy individuals (age ≤ 45y),...
Abstract Background Current methods of amyloid PET interpretation based on the binary classification global signal fail to identify early phases deposition. A recent analysis 18F-florbetapir data from Alzheimer’s disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model regional deposition that resembles neuropathologic estimates and can be used stage an individual’s burden in vivo. Here, we evaluated validity this vivo staging independent older people with subjective...
The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups amyloid-β positive clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 5). All participants underwent neuropsychological assessment tests covering memory,...
Abstract Background We investigated regional amyloid staging characteristics in 11 C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled the Wisconsin Registry Alzheimer’s Prevention. Methods analyzed partial volume effect-corrected distribution ratio maps 220 (mean age = 61.4 years, range 46.9–76.8 years). Regional positivity was established using region-specific thresholds. used four stages frequency-based of characterize individual deposition. Longitudinal...
In previous research we have identified distinct molecular properties underlying regional vulnerability to amyloid deposition and neurodegeneration in AD by studying the respective neuroimaging patterns relation transcriptional architecture of human brain, as determined median gene expression profiles across six brain donors contributing Allen Human Brain Atlas (AHBA). Given that differ individual donors, here examined robustness imaging-genetic associations donor profiles. The brain-wide...
Limbic TDP-43 pathology is a frequent neuropathologic finding in advanced age that associates with hippocampal sclerosis (HS) and can result amnestic deficits mimicking Alzheimer's disease (AD) dementia. Recent imaging-pathologic association studies suggest TDP-43/HS linked to distinct neurodegeneration pattern may be used detect the condition in-vivo. From ADNI autopsy cohort we identified 41 patients clinical diagnosis of MCI or AD dementia at last evaluation availability an FDG-PET scan....
Abstract Elucidating mechanisms underlying the clinical heterogeneity observed among individuals with Alzheimer’s disease (AD) is key to facilitate personalized treatments. We categorized 679 AD into subgroups based on a relative impairment in one cognitive domain (i.e. AD-Memory, AD-Executive-Functioning, AD-Language and AD-Visuospatial-Functioning). compared atrophy patterns derived from MRI identified that closely matched respective profiles, i.e. medial temporal lobe fronto-parietal...
Previously, we have developed an in-vivo staging model of regional amyloid progression based on the frequency amyloid-positivity across cross-sectional Florbetapir-PET scans older individuals. Here refine assessment spread by incorporating regionally varying positivity thresholds into our and assess its consistency in longitudinal PET data. We estimated region-specific signal measured data 13 young controls (age≤45y). then applied these to 179 cognitively normal (CN) ADNI participants...
Previously, we have developed an in-vivo staging model of regional amyloid progression based on the frequency amyloid-positivity across cross-sectional Florbetapir-PET scans older individuals. Here refine assessment spread by incorporating regionally varying positivity thresholds into our and assess its consistency in longitudinal PET data. We estimated region-specific signal measured data 13 young controls (age≤45y). then applied these to 179 cognitively normal (CN) ADNI participants...
Limbic TDP-43 pathology is a frequent neuropathologic finding in advanced age that associates with hippocampal sclerosis (HS) and can result amnestic deficits mimicking Alzheimer's disease (AD) dementia. Recent imaging-pathologic association studies suggest TDP-43/HS linked to distinct neurodegeneration pattern may be used detect the condition in-vivo. From ADNI autopsy cohort we identified 41 patients clinical diagnosis of MCI or AD dementia at last evaluation availability an FDG-PET scan....
Abstract Background Previous studies applied in‐vivo amyloid staging to amyloid‐sensitive PET scans of healthy older people as well patients with Alzheimer’s disease (AD) dementia or mild cognitive impairment characterize stages deposition. We adapted this approach a sample middle‐aged participants at elevated risk for AD due parental history dementia. Method analyzed 11 C‐PiB‐PET 220 enrolled in the Wisconsin Registry Prevention (WRAP) (mean age = 61.4y, range: 46‐76y). Distribution volume...
Abstract Background We investigated regional amyloid staging characteristics in 11 C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled the Wisconsin Registry Alzheimer’s Prevention. Methods analyzed partial volume effect-corrected distribution ratio maps 220 (mean age = 61.4y, range: 46.9-76.8y). Regional amyloid-positivity was established using region-specific thresholds. used four stages frequency-based of characterize individual deposition. Longitudinal...