A5009772791- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Oral microbiology and periodontitis research
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Circadian rhythm and melatonin
- Gut microbiota and health
- Computational Drug Discovery Methods
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Genetics, Aging, and Longevity in Model Organisms
- Salivary Gland Disorders and Functions
- Maritime Navigation and Safety
- Hannah Arendt's Political Philosophy
- Metabolomics and Mass Spectrometry Studies
- Cell Image Analysis Techniques
- Neuroendocrine regulation and behavior
- Genetic Associations and Epidemiology
- Peroxisome Proliferator-Activated Receptors
- Cholinesterase and Neurodegenerative Diseases
- Genetic Mapping and Diversity in Plants and Animals
- 14-3-3 protein interactions
Jackson Laboratory
2018-2024
University of Maine
2020-2024
Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support tooth, microbiome dysbiosis. Currently, there no therapy for reversing disease, treatment generally restricted to preventive measures or tooth extraction. The FDA-approved drug rapamycin slows aging extends lifespan in multiple organisms, including mice. Here, we demonstrate short-term with rejuvenates aged oral cavity elderly mice,...
Alzheimer's disease (AD) is broadly characterized by neurodegeneration, pathology accumulation, and cognitive decline. There considerable variation in the progression of clinical symptoms humans, highlighting importance genetic diversity study AD. To address this, we analyze cell composition amyloid-beta deposition 6- 14-month-old AD-BXD mouse brains. We utilize analytical QUINT workflow- a suite software designed to support atlas-based quantification, which expand deliver highly effective...
Alzheimer disease (AD) has a complex etiology arising from largely unknown interactions between genetic and environmental factors. Even in populations with highly penetrant, disease-causing familial AD mutations, there is wide variation onset progression, suggesting that clinical symptoms are modified by genetics environment. Identification of such modifiers critical, as mechanisms promote resilience to deleterious unhealthy diet, or aging represent promising therapeutic targets for other...
Genetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping identify Dlgap2 as a positional candidate responsible for modifying working memory decline. To evaluate translational relevance this finding, longitudinal measures from human patients, RNA expression post-mortem brain tissue, data genome-wide association study (GWAS) Alzheimer's (AD),...
Many patients with Alzheimer's dementia (AD) also exhibit noncognitive symptoms such as sensorimotor deficits, which can precede the hallmark cognitive deficits and significantly impact daily activities an individual's ability to live independently. However, mechanisms underlying dysfunction in AD their relationship decline remains poorly understood, due part a lack of translationally relevant animal models. To address this, we recently developed novel model genetic diversity disease, AD-BXD...
Summary Alzheimer’s disease (AD), the leading cause of dementia, affects millions people worldwide. With no disease-modifying medication currently available, human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline pathology (amyloid plaques neurofibrillary tangles) present. Remarkably, some individuals who have remain cognitively normal. Uncovering factors that lead to “cognitive resilience” promising path create...
Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others limited no cognitive benefits. Here, we compare the effects of 20% CR, 40% 1-day IF, and 2-day IF feeding paradigms to ad libitum controls on Y-maze working memory (WM) contextual fear (CFM) in a large population Diversity Outbred mice model genetic diversity humans. While CR interventions lifespan, observed enhancement CFM these paradigms, be damaging recall CFM. Using...
Abstract Background Alzheimer’s disease (AD), the leading cause of dementia, affects millions people worldwide. With no disease‐modifying medication currently available, human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline pathology (amyloid plaques neurofibrillary tangles) present. Remarkably, some individuals who have remain cognitively normal. Uncovering factors that lead to “cognitive resilience” promising...
Abstract Background Alzheimer’s disease (AD) is a devastating form of dementia, and its prevalence rising as human lifespan increases. Our lab created the AD‐BXD mouse model, which expresses AD mutations across genetically diverse reference panel (BXD), to identify factors that confer resilience cognitive decline in AD. This model mimics key characteristics including variation age onset severity decline. Method To facilitate discovery conserved mechanisms AD, we generated cross‐species...
Abstract Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support tooth, microbiome dysbiosis. Currently, there no therapy for reversing disease, treatment generally restricted to preventive measures or tooth extraction. The FDA-approved drug rapamycin slows aging extends lifespan in multiple organisms, including mice. Here we demonstrate short-term with rejuvenates aged oral cavity...
Abstract Alzheimer’s disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There significant variation in age at onset severity of symptoms highlighting the importance genetic diversity study AD. To address this, we analyzed cell composition 6- 14-month-old AD-BXD mouse brains using semi-automated workflow (QUINT); which expanded to allow for nonlinear refinement brain atlas-registration, quality control assessment atlas-registration...
Abstract Background The frontal cortex is critical to many cognitive processes and vulnerable pathology neurodegeneration in Alzheimer’s disease. Cortical dysfunction impaired connectivity the have also been observed “normal” age‐related decline, suggesting common mechanisms contributing both AD‐related decline. divergence that may lead AD versus normal aging, however, unclear. Method Here, we used genetically diverse mouse populations modeling either or AD‐BXDs their nontransgenic...
Abstract Background The intersection of genetic diversity, memory, and synaptic function is a critical component in better understanding age‐related cognitive decline. Diversity Outbred mice offer the opportunity to investigate aging across genetically diverse population controlled lab environment. DO exhibit an appreciable amount variance Contextual Fear Memory Acquisition (CFM, CFA), which can be linked individual differences background (Ouellette A. et al, 2022, Cell Reports) . Here, we...
Alzheimer's disease (AD) is complex, with both genetic (G) and environmental (E) factors determining symptom onset progression [1]. Identification of GxE interactions that modulate AD pathogenesis will be critical to developing novel personalized treatments. However, extracting effects challenging in humans due the complexity human genomes difficulty controlling factors. To overcome these barriers, we developed a panel genetically diverse mice carrying familial mutations (AD-BXDs) [2]....
Alzheimer's disease (AD) often presents with multiple non-cognitive comorbidities including sensorimotor deficits, significantly impacting the quality of life for patients and caregivers. Mechanisms underlying these multifactorial symptoms are poorly understood, yet their identification will be critical to find develop effective therapeutic targets. We recently developed a novel panel genetically diverse mice harboring five causal human familial AD mutations (AD-BXDs) have previously...
For a patient diagnosed with Alzheimer's disease, there exist no treatments to prevent, delay, or halt disease progression. Memory impairment and cognitive decline are hallmarks of AD, thus current research has focused predominantly on CNS regions relevant learning memory, such as the hippocampus. However, one most consistently reported non-cognitive phenotypes in AD patients is weight loss, which may precede onset dementia symptoms by much 17 years, raising possibility that dysfunction...
Abstract Many patients with Alzheimer’s dementia also exhibit non-cognitive symptoms such as sensorimotor deficits, which can precede the onset of hallmark cognitive deficits and significantly impact daily activities an individual’s ability to live independently. However, mechanisms underlying dysfunction in AD relationship between decline remain poorly understood, due part a lack translationally relevant animal models. To address this, we recently developed novel model genetic diversity...
Alzheimer's disease (AD) is complex, with both genetic and environmental factors regulating progression. Identification of gene-by-environment interactions that modulate AD pathogenesis critical to understanding mechanisms developing novel, personalized treatments. However, extracting effects challenging in humans due genome complexity difficulty controlling factors, such as diet. We recently developed a panel genetically diverse mice carrying the 5XFAD transgene which contains five human...
Abstract Background An individual’s genetic background plays an important role in governing the risk (or resilience) to developing Alzheimer’s disease (AD) dementia. The goal of this study was identify molecular pathways and cell‐types conferring individual differences cognitive resilience human familial AD (FAD) mutations that drive high amyloid. Method A large set genetically diverse mice harboring (AD‐BXDs) their non‐transgenic littermates (Ntg‐BXDs) were tested for short‐ long‐term...
Abstract Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others limited no cognitive benefits. Here, we compare the effects of 20% CR, 40% 1-day IF, and 2-day IF feeding paradigms to ad libitum controls (AL) on Y-maze working memory contextual fear (CFM) in a large population Diversity Outbred mice model genetic diversity humans. While CR interventions lifespan, observed enhancement CFM these paradigms, be damaging context...
Abstract Background In light of the rising prevalence both diet‐induced obesity and Alzheimer’s Disease (AD) in developed world, influence a high‐fat diet (HFD) on AD progression was investigated. Beta‐amyloid 1‐42 (Aβ42), particular, examined as little is known about extent to which an individual’s genetics, sex, determine onset this classic neuropathology. Method AD‐BXD mice were generated by crossing female 5XFAD male members BXD reference panel (Neuner, et al. 2019). Cortical Aβ42 levels...