A5084740171- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Cerebrovascular and genetic disorders
- Cerebrovascular and Carotid Artery Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Advanced Neuroimaging Techniques and Applications
- Functional Brain Connectivity Studies
- Extracellular vesicles in disease
- Intracerebral and Subarachnoid Hemorrhage Research
- Amyotrophic Lateral Sclerosis Research
- Cardiovascular Health and Disease Prevention
- Tryptophan and brain disorders
- Acute Ischemic Stroke Management
- S100 Proteins and Annexins
- Moyamoya disease diagnosis and treatment
- Traumatic Brain Injury and Neurovascular Disturbances
- Retinal Imaging and Analysis
- Atherosclerosis and Cardiovascular Diseases
- Health, Environment, Cognitive Aging
- Barrier Structure and Function Studies
- Parkinson's Disease Mechanisms and Treatments
- Blood Pressure and Hypertension Studies
- Cognitive Functions and Memory
- Prion Diseases and Protein Misfolding
Icahn School of Medicine at Mount Sinai
2011-2025
James J. Peters VA Medical Center
2023-2025
University Memory and Aging Center
2016-2024
University of California, San Francisco
2017-2024
Allen Institute for Brain Science
2022-2024
Indiana University School of Medicine
2024
Mount Sinai Hospital
2024
Center for Neurosciences
2020-2023
San Francisco VA Medical Center
2017-2023
Montefiore Health System
2023
We investigated plasma proteomic markers of astrocytopathy, brain degeneration, plasticity, and inflammation in sporadic early-onset versus late-onset Alzheimer's disease (EOAD LOAD).
The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In study, we evaluated FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain DMN subnetworks were assessed: (1) within-DMN, (2) between anterior...
Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on from 45 cognitively normal subjects ranging 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes age. then compared this cohort 14 impaired subjects. In subjects, downregulation occurred concomitantly cytokine signaling CD8 T cells. Clonal...
Abstract Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant atrophy show severe anomia and verbal semantic deficits meet criteria for variant primary progressive aphasia dementia, early are more difficult to diagnose as their symptoms less well understood. is associated prominent emotional behavioural changes, meet, go on frontotemporal dementia. Uncertainty around absence of an overarching...
Mutations in the FOXP2 gene cause a severe communication disorder involving speech deficits (developmental verbal dyspraxia), accompanied by wide-ranging impairments expressive and receptive language. The protein encoded belongs to divergent subgroup of forkhead-box transcription factors, with distinctive DNA-binding domain motifs that mediate hetero- homodimerization. Here we report first direct functional genetic investigation missense nonsense mutations using human cell-lines, including...
To determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers neurologically healthy older adults.We analyzed concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), total (t-tau) among 132 normal adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes a measure episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses...
Neuron-derived exosomes (NDEs) were enriched by anti-L1CAM antibody immunoabsorption from plasmas of subjects ages 18–26 yr within 1 wk after a sports-related mild traumatic brain injury (acute mTBI) (n = 18), 3 mo or longer the last 2–4 mTBIs (chronic 14) and with no recent history TBI (controls) 21). Plasma concentrations NDEs, assessed counts levels extracted exosome marker CD81, significantly depressed mean 45% in acute mTBI (P < 0.0001), but not chronic mTBI, compared controls. Mean...
Levels of complement proteins (CPs) in plasma astrocyte-derived exosomes (ADEs) that are abnormal Alzheimer's disease (AD) have not been assessed mild cognitive impairment (MCI).Participants (n = 20 per group) had either MCI converting to dementia within 3 years (MCIC), remaining stable over (MCIS), disease, or were controls. CPs ADEs isolated from plasmas by anti-human glutamine aspartate transporter antibody absorption quantified ELISAs.ADE levels C1q and C4b the classical pathway, factor...
Frontotemporal dementia refers to a group of progressive neurodegenerative syndromes usually caused by the accumulation pathological tau or TDP-43 proteins. The effects these proteins in brain are complex, and each can present with several different clinical syndromes. Clinical efficacy trials drugs targeting must use endpoints that meaningful all participants despite variability symptoms across patients. There many candidate measures, including neuropsychological scores functional measures....
Abstract Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer’s disease (AD), suggesting Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed classifying However, it remains unclear whether disturbances in each arm A/T/N framework contribute equally throughout progression Here, using random forest machine learning method analyze participants...
The concept of vascular contributions to cognitive impairment and dementia (VCID) derives from more than two decades research indicating that (1) most older individuals with have post mortem evidence multiple contributing pathologies (2) along the preeminent role Alzheimer's disease (AD) pathology, cerebrovascular accounts for a substantial proportion this contribution. Contributing processes include both overt strokes caused by etiologies such as large vessel occlusion, cardioembolism,...
High-performing biomarkers measuring the vascular contributions to cognitive impairment and dementia are lacking.
Importance Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers trial recruitment success, but no such tools validated for FTLD. Objective To evaluate the reliability validity of measures remote FTLD evaluations. Design, Setting, Participants In this cohort study conducted from...
Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI critical for comprehending disease progression and enabling preventative intervention.
Objective: To determine the longitudinal relationship between MCP-1/CCL2 and memory function in older adults. Methods: We examined plasma levels a verbal measure (CVLT-II 20' recall) sample of 399 asymptomatic adults (mean age=72.1). Total visits ranged from 1 to 8, with an average time 2.1 years each visit, yielding 932 total observations. In order isolate change over time, we decomposed into subject-specific means deviations mean. The variables were entered as predictors linear mixed...
Abstract Cerebral perfusion declines across the lifespan and is altered in early stages of several age‐related neuropathologies. Little known, however, about longitudinal evolution healthy older adults, particularly when quantified using magnetic resonance imaging with arterial spin labeling (ASL). The objective was to characterize typically aging adults elucidate associations cognition brain structure. Adults who were functionally intact at baseline ( n = 161, ages 47–89) underwent ASL...
Background: Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer’s disease (AD). Objective: To examine associations between GFAP Aβ deposition older adults across the typical aging-to-AD dementia spectrum. Methods: We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, 37) covering spectra of clinical severity (CDR Sum Boxes; CDR-SB) Aβ-PET burden. was completed with either...