A5068688487- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Prion Diseases and Protein Misfolding
- Computational Drug Discovery Methods
- Cellular transport and secretion
- Neurological Disease Mechanisms and Treatments
- S100 Proteins and Annexins
- Memory and Neural Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Bioinformatics and Genomic Networks
- Advanced Neuroimaging Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Functional Brain Connectivity Studies
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- Neurological diseases and metabolism
- Genetic Associations and Epidemiology
- Health Systems, Economic Evaluations, Quality of Life
- Nerve injury and regeneration
Harvard University
2016-2025
Massachusetts General Hospital
2016-2025
MaineGeneral Medical Center
2016-2025
Harvard NeuroDiscovery Center
2011-2024
Federal Reserve
2024
Boston University
1996-2024
Memorial Hermann–Texas Medical Center
2024
University of Georgia
2024
Carnegie Mellon University
1996-2024
John Wiley & Sons (United States)
1996-2024
The National Institute on Aging and the Alzheimer's Association charged a workgroup with task of revising 1984 criteria for disease (AD) dementia. sought to ensure that revised would be flexible enough used by both general healthcare providers without access neuropsychological testing, advanced imaging, cerebrospinal fluid measures, specialized investigators involved in research or clinical trial studies who have these tools available. We present all‐cause dementia AD retained framework...
Abstract A consensus panel from the United States and Europe was convened recently to update revise 1997 guidelines for neuropathologic evaluation of Alzheimer's disease (AD) other diseases brain that are common in elderly. The new recognize pre‐clinical stage AD, enhance assessment AD include amyloid accumulation as well neurofibrillary change neuritic plaques, establish protocols Lewy body disease, vascular injury, hippocampal sclerosis, TDP‐43 inclusions, recommend standard approaches...
We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer9s disease patients who had been examined during life. counted NFTs SPs 13 cytoarchitectural regions representing limbic, primary sensory, association cortices, subcortical neurotransmitter-specific areas. The degree neuropathologic change was compared with severity dementia, as assessed by Blessed Dementia Scale duration illness. found that (1) dementia positively related to number...
Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern pathology the subiculum hippocampal formation and layers II IV entorhinal cortex. The affected cells are precisely those that interconnect with association cortices, basal forebrain, thalamus, hypothalamus, crucial to memory. This focal isolates much its input output probably contributes memory disorder in patients.
Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in brains of patients with neurodegenerative diseases and have been implicated mediating neuronal death cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, loss, behavioral impairments. After suppression transgenic tau, memory function recovered, neuron numbers stabilized, but to our surprise, NFTs continued accumulate. Thus, not sufficient...
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified genetic sharing 25 disorders from genome-wide association studies 265,218 patients 784,643 control participants assessed relationship to 17 phenotypes 1,191,588 individuals. Psychiatric common variant risk, whereas neurological appear more distinct one another psychiatric disorders. also identified significant between a number...
The entorhinal cortex (EC) plays a crucial role as gateway connecting the neocortex and hippocampal formation. Layer II of EC gives rise to perforant pathway, major source excitatory input hippocampus, layer IV receives efferent projection. is affected severely in Alzheimer disease (AD), likely contributing memory impairment. We applied stereological principles neuron counting determine whether neuronal loss occurs very early stages AD. studied 20 individuals who at death had Clinical...
Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images the resolution detail standard histology without use exogenous stains. Imaging indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, collagen provides crucial information for physiology pathology. The efficient application multiphoton to imaging requires knowledge...
Abstract To assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted number of neurons, senile plaques, neurofibrillary tangles a high‐order association cortex. We studied superior temporal sulcus 34 individuals with AD 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The neurons subjects was stable across sixth to ninth decades. In AD, more than 50% were lost. Both loss...
The distribution of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) was mapped in 39 cortical areas 11 brains patients with Alzheimer's disease (AD). Whole hemisphere blocks were embedded polyethylene glycol (Carbowax), sectioned coronally, stained thioflavin S thionin. densities NFTs NPs assessed using a numerical rating scale for each area. Scores grouped by type cortex lobe statistical analysis. Highly significant differences obtained. For example, limbic periallocortex...
The sirtuins are members of the histone deacetylase family proteins that participate in a variety cellular functions and play role aging. We identified potent inhibitor sirtuin 2 (SIRT2) found inhibition SIRT2 rescued alpha-synuclein toxicity modified inclusion morphology model Parkinson's disease. Genetic via small interfering RNA similarly toxicity. Furthermore, inhibitors protected against dopaminergic cell death both vitro Drosophila results suggest link between neurodegeneration
Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable vivo using magnetic resonance imaging. It not clear whether abnormalities cortical anatomy AD can be reliably measured across different subject samples, how closely they track symptoms, are prior to symptoms. An exploratory map thinning mild was used define interest that were applied a hypothesis-driven fashion other samples. Results demonstrate...
The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, has been shown specific ligand for number different receptors and other molecules, transported by complex trafficking pathways, modulated in response variety environmental stressors, able induce pro-inflammatory activities.Here, we provide data supporting vivo function...