David M. Holtzman

This study shows that reducing APOE4 in vascular-associated fibroblasts decreases cerebral amyloid angiopathy and improves vascular function in a mouse model.

This study shows that an engineered bacterium worsens neurodegeneration in a tauopathy mouse model by altering immune responses, while the unmodified strain has no effect.

This study shows that fingolimod worsens T cell infiltration and tau pathology in a mouse model of tauopathy, despite reducing peripheral T cells.

This study shows that loss of Ms4a4a remodels microglial transcriptional programs and reduces dense-core plaque-associated tau spreading in a mouse model of Alzheimer's disease.

This study investigates how early binding of anti-amyloid antibodies to cerebral amyloid angiopathy (CAA) drives complement activation, inflammation, and ARIA in Alzheimer's disease mouse models.

This study shows that cDC1 cells prime CD8+ T cells, which then exacerbate tau-mediated neurodegeneration in mice.

This study creates a multi-modal atlas of choroid plexus pathology across aging and Alzheimer's disease, identifying fibrosis, calcification, and macrophage abnormalities as key features.

The paper investigates cell-to-cell communication in Alzheimer's disease to characterize disease biology and suggest new avenues for therapeutic intervention.

This study combines APOE4 and TREM2R47H in female tauopathy mice to identify pathways activated by AD risk factors, finding cGAS-STING signaling and microglial senescence as potential drivers.

This study uses 3D direct neuronal reprogramming of AD patient fibroblasts to recapitulate AD neuropathology, showing A{beta} deposition, tauopathy, and neuronal death, and identifies potential therapeutic targets.

The paper shows that apoE isoforms modulate Aβ aggregation, clearance, and toxicity in Alzheimer's disease, with implications for therapeutic strategies.

This paper shows that APOE2 gene therapy reduces amyloid deposition, neurodegeneration, and microglial activation in an Alzheimer's mouse model with ongoing APOE4 expression.

This study shows that Ch25h/25HC promotes neuroinflammation and neurodegeneration in a tauopathy mouse model by enhancing proinflammatory signaling and impairing sterol synthesis.

This study shows that tauopathy disrupts network-level homeostatic set-points in hippocampal activity but not individual neuron activity, with implications for computational capacity and behavior.

The paper maps sleep oscillatory events as biomarkers for early Alzheimer's disease by analyzing EEG and CSF biomarkers in aging adults.

This study shows ApoE isoforms modulate neuroproteasome function, affecting Tau aggregation thresholds and contributing to Alzheimer's disease pathology.

This study shows that acute hyper- and hypoglycemia disrupt the metabolic cooperation between glucose and lactate in the brain, affecting sleep-wake cycles.

This study shows that Kir6.2-KATP channels are necessary for hyperglycemia-induced increases in amyloid-beta and Alzheimer's pathology by regulating lactate transport and Aβ release.

The paper shows astrocyte-derived cholesterol regulates amyloid precursor protein trafficking to lipid rafts, affecting Aβ and sAPP production in neurons, and disrupting cholesterol synthesis reduces amyloid pathology in mice.

This study shows that sulfonylureas reduce Alzheimer's pathology by targeting vascular KATP channels, decreasing amyloid-beta aggregation and improving vascular function in mice.

This study shows that 25-HC enhances IL-1β production in microglia, particularly in apoE4-expressing cells, suggesting a role in AD neuroinflammation.

This paper introduces SEQUIN, a super-resolution imaging workflow for analyzing synapses, and shows synapse loss in traumatic brain injury and Alzheimer's models.

This study shows that a high-salt diet causes cognitive impairment in mice through tau hyperphosphorylation, which is prevented by restoring nitric oxide production.

This study uses single-nuclei RNA-seq to compare cell proportions and gene expression in Mendelian and sporadic AD brains, identifying reduced excitatory neurons in a Mendelian carrier and proposing best practices for analysis.

This study identifies dysregulation of cholesterol and matrisome pathways in human APOE ε4 glia, linking them to Alzheimer's disease risk.

The paper constructs polygenic risk scores for sporadic late-onset Alzheimer's Disease and finds shared genetic architecture with familial and early-onset forms, showing varying odds ratios across cohorts.