Lance A. Johnson
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View article: Knockout of Perilipin-2 in Microglia Alters Lipid Droplet Accumulation and Response to Alzheimer’s Disease Stimuli
Knockout of Perilipin-2 in Microglia Alters Lipid Droplet Accumulation and Response to Alzheimer’s Disease Stimuli Open
Lipid droplets (LDs) are emerging as key regulators of metabolism and inflammation, with their buildup in microglia linked to aging and neurodegeneration. Perilipin-2 (Plin2) is a ubiquitously expressed LD-associated protein that stabilize…
View article: APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition
APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition Open
Compared to individuals carrying two copies of the ε4 allele of apolipoprotein E (APOE), ε2 homozygotes have an approximate 99% reduction in late-onset Alzheimer's disease (AD) risk. Here we develop a knock-in model that allows for an indu…
View article: Clonal expansion of cytotoxic CD8<sup>+</sup> T cells in lecanemab-associated ARIA
Clonal expansion of cytotoxic CD8<sup>+</sup> T cells in lecanemab-associated ARIA Open
Amyloid-related imaging abnormalities (ARIA) remain the principal safety concern limiting adoption of anti-amyloid therapies such as lecanemab, yet their underlying biology is poorly defined. To address this, we performed deep multi-omic p…
View article: Knockout of Perilipin-2 in Microglia Alters Lipid Droplet Accumulation and Response to Alzheimer’s Disease Stimuli
Knockout of Perilipin-2 in Microglia Alters Lipid Droplet Accumulation and Response to Alzheimer’s Disease Stimuli Open
Lipid droplets (LDs) are emerging as critical regulators of cellular metabolism and inflammation, with their accumulation in microglia linked to aging and neurodegeneration. Perilipin 2 (Plin2) is a ubiquitously expressed LD-associated pro…
View article: Tau pathology reprograms glucose metabolism to support glutamatergic activity and excitatory imbalance
Tau pathology reprograms glucose metabolism to support glutamatergic activity and excitatory imbalance Open
Alzheimer’s disease (AD) is not only characterized by amyloid-beta (Aβ) and tau pathology, but also by early and progressive disruptions in metabolism. Neuronal excitability is tightly coupled with metabolic demand, and aberrant excitatory…
View article: APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses
APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses Open
View article: High-Resolution Spatial Profiling of Microglia Reveals Proximity Associated Immunometabolic Reprogramming in Alzheimer’s Disease
High-Resolution Spatial Profiling of Microglia Reveals Proximity Associated Immunometabolic Reprogramming in Alzheimer’s Disease Open
Single-cell RNA sequencing has demonstrated that the presence of parenchymal amyloid plaques and intracellular hyperphosphorylated tau pathology is associated with distinctive (and possibly disease-driving) microglial heterogeneity. Howeve…
View article: Genomic and cellular context-dependent expression of the human ELMO1 gene transcript variants
Genomic and cellular context-dependent expression of the human ELMO1 gene transcript variants Open
View article: ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep
ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep Open
Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are associated with wakefulness and decrease…
View article: <i>APOE4</i> alters the lipid droplet proteome and modulates droplet dynamics
<i>APOE4</i> alters the lipid droplet proteome and modulates droplet dynamics Open
Excess lipid droplet (LD) accumulation is associated with several pathological states, including Alzheimer’s disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics contribute to pathophysiology of these dis…
View article: Lipid Droplet Dynamics are Modulated by Age and APOE Genotype
Lipid Droplet Dynamics are Modulated by Age and APOE Genotype Open
Background Aging microglia accumulate lipid droplets (LDs), secrete pro‐inflammatory cytokines, and are defective in phagocytosis. The E4 allele of Apolipoprotein E ( APOE ) is the strongest genetic risk factor for late‐onset Alzheimer’s d…
View article: AD pathology‐independent effects of astrocyte‐ or microglia‐specific replacement of APOE4 with APOE2
AD pathology‐independent effects of astrocyte‐ or microglia‐specific replacement of APOE4 with APOE2 Open
Background Compared with the E3 allele of Apolipoprotein E (APOE), E4 increases late‐onset Alzheimer’s Disease (AD) risk up to 15‐fold, while the E2 allele substantially decreases risk. In the CNS, ApoE is predominantly synthesized by astr…
View article: Validation of Various Pan‐ApoE and Isoform‐Specific ApoE Antibodies
Validation of Various Pan‐ApoE and Isoform‐Specific ApoE Antibodies Open
Background Apolipoprotein E (ApoE) exists in three protein isoforms: E2, E3, and E4, which differ by only one or two amino acids. These slight differences profoundly effect protein structure and function, allowing each isoform to different…
View article: <i>APOE4</i> to <i>APOE2</i> ‘Switching’ in Astrocytes Alters the Cerebral Transcriptome and Decreases AD Neuropathology at Different Points on the AD Pathophysiological Timeline
<i>APOE4</i> to <i>APOE2</i> ‘Switching’ in Astrocytes Alters the Cerebral Transcriptome and Decreases AD Neuropathology at Different Points on the AD Pathophysiological Timeline Open
Background Compared to the ‘neutral’ E3, the E4 allele of Apolipoprotein E ( APOE ) confers up to a 15‐fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by a similar degree. Here, w…
View article: Alzheimer’s and metabolism wed with IDO1
Alzheimer’s and metabolism wed with IDO1 Open
Kynurenine pathway inhibition reverses deficits in Alzheimer’s mouse models
View article: Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference
Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference Open
INTRODUCTION The apolipoprotein E gene ( APOE ) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid‐beta and tau pathologi…
View article: Enhancement of high-density lipoprotein-associated protease inhibitor activity prevents atherosclerosis progression
Enhancement of high-density lipoprotein-associated protease inhibitor activity prevents atherosclerosis progression Open
View article: Sex and <i>APOE</i> genotype influence respiratory function under hypoxic and hypoxic-hypercapnic conditions
Sex and <i>APOE</i> genotype influence respiratory function under hypoxic and hypoxic-hypercapnic conditions Open
This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer’s model. Both sex and genotype …
View article: 369 Investigating the impact of bariatric surgery on metabolic mechanisms that promote obesity-associated inflammation in subjects with and without Type 2 Diabetes
369 Investigating the impact of bariatric surgery on metabolic mechanisms that promote obesity-associated inflammation in subjects with and without Type 2 Diabetes Open
OBJECTIVES/GOALS: This project will provide novel insights into mechanism(s) by which differences in inflammation develop & resolve, or fail to resolve, in metabolically different groups of bariatric surgery patients determined by Type 2 D…
View article: Kir6.2-K<sub>ATP</sub>channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis
Kir6.2-K<sub>ATP</sub>channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis Open
Summary Metabolism plays an important role in the maintenance of vigilance states (e.g. wake, NREM, and REM). Brain lactate fluctuations are a biomarker of sleep. Increased interstitial fluid (ISF) lactate levels are necessary for arousal …
View article: Mid‐life APOE4 to APOE2 ‘Switching’ Alters the Cerebral Transcriptome and Lipidome in a Transgenic Mouse Model
Mid‐life APOE4 to APOE2 ‘Switching’ Alters the Cerebral Transcriptome and Lipidome in a Transgenic Mouse Model Open
Background Compared to the ‘neutral’ E3, the E4 allele of Apolipoprotein E (APOE) confers up to a 15‐fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by a similar degree. APOE’s st…
View article: LDs in AD: Lipid Droplet Dynamics are Modulated by APOE
LDs in AD: Lipid Droplet Dynamics are Modulated by APOE Open
Background Aging microglia accumulate lipid droplets (LDs), secrete pro‐inflammatory cytokines, and are defective in phagocytosis. The E4 allele of Apolipoprotein E (APOE) is the strongest genetic risk factor for late‐onset Alzheimer’s dis…
View article: APOE genotype modifies microglial immunometabolism
APOE genotype modifies microglial immunometabolism Open
Background Metabolic dysfunction and neuroinflammation characterize Alzheimer’s disease (AD), but it is unclear if these two facets of the disease are linked. The E4 allele of Apolipoprotein E (APOE) is the strongest genetic risk factor fo…
View article: Glia‐Selective Replacement of APOE4 with APOE2: Implications for AD‐Associated Pathologies
Glia‐Selective Replacement of APOE4 with APOE2: Implications for AD‐Associated Pathologies Open
Background Compared to the ‘neutral’ E3, the E4 allele of Apolipoprotein E (APOE) confers up to a 15‐fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by a similar degree. APOE’s st…
View article: ApoE isoform does not influence skeletal muscle regeneration in adult mice
ApoE isoform does not influence skeletal muscle regeneration in adult mice Open
Introduction: Apolipoprotein E (ApoE) has been shown to be necessary for proper skeletal muscle regeneration. Consistent with this finding, single-cell RNA-sequencing analyses of skeletal muscle stem cells (MuSCs) revealed that Apoe is a t…
View article: Deconvolution reveals cell-type-specific transcriptomic changes in the aging mouse brain
Deconvolution reveals cell-type-specific transcriptomic changes in the aging mouse brain Open
View article: Apolipoprotein E genotype affects innate susceptibility to <i>Listeria monocytogenes</i> infection in aged male mice
Apolipoprotein E genotype affects innate susceptibility to <i>Listeria monocytogenes</i> infection in aged male mice Open
Apolipoprotein E (ApoE) is a lipid transport protein that is hypothesized to suppress proinflammatory cytokine production, particularly after stimulation with Toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS). Studies using…
View article: Enhancement of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression
Enhancement of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression Open
Background Inflammatory cells within atherosclerotic lesions secrete various proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. The relative contributions o…
View article: DNA-AgNC Loaded Liposomes for Measuring Cerebral Blood Flow Using Two-Photon Fluorescence Correlation Spectroscopy
DNA-AgNC Loaded Liposomes for Measuring Cerebral Blood Flow Using Two-Photon Fluorescence Correlation Spectroscopy Open
Unraveling the transport of drugs and nanocarriers in cerebrovascular networks is important for pharmacokinetic and hemodynamic studies but is challenging due to the complexity of sensing individual particles within the circulatory system …
View article: APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge Open