A5042247598- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Dementia and Cognitive Impairment Research
- Neurological Disease Mechanisms and Treatments
- Machine Learning in Healthcare
- Single-cell and spatial transcriptomics
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- S100 Proteins and Annexins
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Acute Ischemic Stroke Management
- Tryptophan and brain disorders
- Chronic Disease Management Strategies
- GDF15 and Related Biomarkers
- Immune cells in cancer
- Computational Drug Discovery Methods
- Biomedical Text Mining and Ontologies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Health, Environment, Cognitive Aging
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurological disorders and treatments
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
Harvard University
2013-2025
Massachusetts General Hospital
2015-2025
MaineGeneral Medical Center
2011-2024
Alzheimer’s Disease Neuroimaging Initiative
2022-2023
New York University
2021-2023
Harvard University Press
2022
Institute on Aging
2022
National Institute on Aging
2022
University of Massachusetts Amherst
2016-2021
University of Iowa Hospitals and Clinics
2013-2017
In Alzheimer disease (AD), deposition of neurofibrillary tangles and loss synapses in the neocortex limbic system each correlate strongly with cognitive impairment. Tangles are composed misfolded hyperphosphorylated tau proteins; however, link between abnormalities synaptic dysfunction remains unclear. We examined location control AD cortices using biochemical morphologic methods. found that, addition to its well-described axonal localization, normal is present at both presynaptic...
Clinico-pathological correlation studies and positron emission tomography amyloid imaging have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype these unique cases might prove relevant to understanding human resilience pathology. We conducted detailed quantitative histopathological biochemical assessments on from non-demented before death whose were...
Abstract Mitochondria contribute to shape intraneuronal Ca 2+ signals. Excessive taken up by mitochondria could lead cell death. Amyloid beta (Aβ) causes cytosolic overload, but the effects of Aβ on mitochondrial levels in Alzheimer’s disease (AD) remain unclear. Using a ratiometric indicator targeted neuronal and intravital multiphoton microscopy, we find increased associated with plaque deposition death transgenic mouse model cerebral β-amyloidosis. Naturally secreted soluble applied onto...
The apolipoprotein E ε4 gene is the most important genetic risk factor for sporadic Alzheimer’s disease, but link between this and neurodegeneration remains unclear. Using array tomography, we analysed >50 000 synapses in brains of 11 patients with disease five non-demented control subjects found that synapse loss around senile plaques correlates burden oligomeric amyloid-β neuropil synaptotoxic oligomerized peptide present at a subset synapses. Further analysis reveals have significantly...
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in brain pathological hallmark AD, but oligomeric, soluble forms Aβ have been implicated synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele known to be a genetic risk factor for developing AD. However, it still unknown how apoE impacts process oligomerization. Here, we found that level oligomers APOE ε4/ε4 AD...
Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration Alzheimer's disease (AD). Damaged mitochondria are one of main sources reactive oxygen species and accumulate Aβ plaque-associated dystrophic neurites AD brain. Although causes neuronal vitro, this has never been directly observed vivo living mouse Here, we tested for first time whether plaques soluble oligomers induce mitochondrial surrounding neurons vivo, neurotoxic...
Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to deposits or just reacting plaque-associated neuritic damage remains elusive. We postulate may differentially respond fibrillar β. Therefore, we quantified the size distribution of thioflavin-S (ThioS)-positive temporal neocortex 40 AD patients microglial astrocyte responses their vicinity (≤50 μm) performed correlations between both...
While accumulation of amyloid-β (Aβ) deposited as senile plaques is a hallmark feature Alzheimer's disease (AD), the neurotoxicity these deposits remains controversial. Recent in vitro studies suggested link between elevated Aβ and mitochondrial dysfunction that might contribute to pathogenesis AD. However, vivo evidence for mitochondria caused by still missing. Using intravital multiphoton imaging with range fluorescent markers, we systematically surveyed structural functional changes AD...
Classical immunohistochemical studies in the Alzheimer disease (AD) brain reveal prominent glial reactions, but whether this pathological feature is due primarily to cell proliferation or a phenotypic change of existing resting cells remains controversial. We performed double-fluorescence astrocytes and microglia, followed by unbiased stereology-based quantitation temporal cortex 40 AD patients 32 age-matched nondemented subjects. Glial fibrillary acidic protein (GFAP) major...
Objective The Alzheimer disease (AD) APOE ε4 risk allele associates with an earlier age at onset and increased amyloid‐β deposition, whereas the protective ε2 delays appears to prevent deposition. Yet clinical pathological effects of remain uncertain because its relative rarity. We investigated alleles on AD pathology cognition in a large US data set well‐characterized patients. Methods studied individuals from National Alzheimer's Coordinating Center autopsy cohort across entire...
Anti-amyloid-b immunization leads to amyloid clearance in patients with Alzheimer's disease, but the effect of vaccination on amyloid-b-induced neuronal pathology has not been quantitatively examined.The objectives this study were address effects anti-amyloid-b active neurite trajectories and pathological hallmarks disease human hippocampus.Hippocampal sections from five enrolled AN1792 Phase 2a trial compared those 13 non-immunized Braak-stage age-matched eight non-demented...
The accumulation of neurofibrillary tangles in Alzheimer's disease (AD) propagates with characteristic spatiotemporal patterns which follow brain network connections, implying trans-synaptic transmission tauopathy. Since misfolded tau has been shown to transmit across synapses AD animal models, we hypothesized that patients may contain tau. By immunofluorescence imaging bipartite from subjects, detected protein 38.4% presynaptic and 50.9% postsynaptic terminals. pre/post distribution for...
It has long been assumed that β-amyloid (Aβ) had to assemble into fibrillar amyloid plaques exert its neurotoxic effects in Alzheimer disease. An alternative hypothesis is soluble oligomers ofAβ play a much larger role neuronal damage than the insoluble component. We have tested these competing hypotheses vivo by studying clinicopathologic correlates of oligomeric Aβ species and classic brains double-transgenic APP-tau mice up 17 months age. Biochemical immunohistochemical measures brain...