Joshua Keene

Neuroscience · Neuroinflammation · Alzheimer's Disease · Aging

Joshua Keene, PhD

Preclinical neuroscientist specializing in peripheral immune activation as a modifiable contributor to tau pathology and neuroinflammation in Alzheimer's disease models. Doctoral research conducted across two institutions: Central Michigan University with Dr. Gary Dunbar, and Michigan State University's Grand Rapids Research Center with Drs. David Morgan and Marcia Gordon.

2.8×
Hippocampal p-tau increase vs. vehicle controls
at 30 days post-PAMP challenge in PS19 mice
46% / 59%
Less hippocampal amyloid plaque in male / female 5xFAD offspring of 5xFAD vs. Non-Tg dams
150+
Animals across doctoral research cohorts
PS19 and 3xTg
30+
Undergraduate and medical students
trained and mentored

Doctoral & Master's Work

Research

Doctoral Research · PAMP-Induced Tau Pathology & Neuroinflammation

I examined whether repeated challenges with diverse peripheral immune stimuli drive tau pathology and neuroinflammation in PS19 tauopathy mice, with tissue collected 30 days after the final challenge to assess longer-term consequences of immune activation.

Primary Finding

  • PAMP administration increased hippocampal p-tau (AT8) 2.8-fold and whole-hemisphere p-tau 3.0-fold, while total tau (HT7) remained unchanged.

Supporting Finding

  • A synergistic genotype × treatment interaction for MHC II and positive correlations between p-tau and glial reactivity markers support a relationship between peripheral immune activation, tau pathology, and neuroinflammation.
PS19 PAMP study experimental timeline injection schedule behavioral testing tissue collection
Study design · PS19 tauopathy model
AT8 p-tau hippocampus PAMP vs vehicle PS19 mice with dot plot and high magnification insets
p-tau (AT8) in PS19 mice · hippocampus · PAMPs vs. vehicle
Spearman correlation matrix p-tau glial markers and behavioral measures PS19 PAMPs group hippocampus
Spearman correlation matrix in PAMP-treated PS19 mice · hippocampus · tau, glial markers, and behavior
Dissertation (PDF)

Master's Thesis · Maternal 5xFAD Genotype, Amyloid Deposition, and Microglial Density

I examined whether maternal 5xFAD genotype, a proposed source of prenatal inflammatory stress, alters amyloid plaque deposition and microglial density in 5xFAD offspring, comparing mice born to 5xFAD versus Non-Tg dams and assessing sex differences in these effects.

Primary Finding

  • Offspring of 5xFAD dams showed 46% (male) and 59% (female) less hippocampal amyloid plaque (6E10) than offspring of Non-Tg dams.

Supporting Finding

  • Maternal genotype did not alter microglial density despite the reduction in plaque burden, suggesting altered amyloid pathology independent of microglial quantity.
Breeding paradigm schematic showing reciprocal 5xFAD crosses, F1 offspring genotyping, tissue collection at 4 months, and stereological analysis
Study design · 5xFAD prenatal exposure model
Iba1 microglia and 6E10 amyloid in female 5xFAD hippocampus from Non-Tg versus 5xFAD dams
Microglia (Iba1) and amyloid (6E10) in 5xFAD mice · hippocampus · 5xFAD vs. Non-Tg dams · Scale bars = 200 µm
Hippocampal plaque area by maternal genotype in male and female 5xFAD offspring
Plaque area (6E10) in 5xFAD mice · hippocampus · 5xFAD vs. Non-Tg dams
Master's Thesis (PDF)

Manuscripts

Publications

Conference Presentations

Posters

Click any poster to open the full PDF.

2023 MISfN poster: Inflammatory Stress Contributes to Tau Pathology in the PS19 Mouse Model of Alzheimer's Disease
Inflammatory Stress Contributes to Tau Pathology in the PS19 Mouse Model of Alzheimer's Disease Michigan Society for Neuroscience (MISfN) · MSU, East Lansing, MI · 2023 Repeated and varied infection mimetic administration increases hippocampal phosphorylated tau (AT8) and astrocyte reactivity (GFAP) in PS19 mice.
2022 SCREE poster: Peripheral Inflammation and Physiological Hallmarks of Alzheimer's Disease
Peripheral Inflammation and Physiological Hallmarks of Alzheimer's Disease Student Creative and Research Endeavors Exhibition (SCREE) · CMU · 2022 Examining the effects of multiple and varied PAMP administration on phosphorylated and total tau, glial reactivity, and behavior in the PS19 tauopathy model.
2019 SCREE poster: Effects of Inflammatory Stress During the Asymptomatic Phase of Alzheimer's Disease
Effects of Inflammatory Stress During the Asymptomatic Phase of Alzheimer's Disease SCREE · CMU · 2019 5xFAD offspring of 5xFAD dams showed reduced hippocampal amyloid burden, with no effect on microglial density.
2018 SCREE poster: Role of Prenatal Exposure to Inflammatory Stress on Microglia Density and Amyloidogenesis
Role of Prenatal Exposure to Inflammatory Stress on Microglia Density and Amyloidogenesis SCREE · CMU · 2018 5xFAD offspring of 5xFAD dams showed reduced hippocampal amyloid burden, while microglial density remained unchanged.
2018 MISfN poster: The Role of Inflammation and Sex on Dendritic Spines and Neuron Arborization in NL-G-F Mice
The Role of Inflammation and Sex on Dendritic Spines and Neuron Arborization in NL-G-F Mice (co-author) MISfN · 2018 Examining the effects of repeated LPS administration on dendritic spine density and neuron arborization in the NL-G-F knock-in model.
2017 MISfN/SCREE poster: Role of Neuroinflammation and Sex Differences in Alzheimer's Disease
Role of Neuroinflammation and Sex Differences in Alzheimer's Disease MISfN / SCREE · 2017 Examining the effect of prenatal chronic inflammation exposure on amyloid plaque burden and microglial density using the 5xFAD model of Alzheimer's disease.
2016 MISfN poster: Cannabinoid Agonist WIN-55,212-2 Modulation of Bone Derived Mesenchymal Stem Cells
Cannabinoid Agonist WIN-55,212-2 Modulation of Bone Derived Mesenchymal Stem Cells MISfN · 2016 The cannabinoid agonist WIN 55,212-2 produces a biphasic effect on MSC proliferation, peaking at 1 µM relative to vehicle and 10 µM.

Methods & Expertise

Technical Skills

Animal Models

PS19 5xFAD APP-KI NL-F / NL-G-F 3xTg MAPT-KI

LRRK1/LRRK2-KO Parkinson's models; doxycycline-regulated (Tet-Off) TAg/OFF neuronal cell-cycle re-entry; AAV-mediated human tau seeding (bilateral hippocampus and anterior cortex).

Surgical & In Vivo Procedures

Stereotaxic surgery AAV delivery Transcardial perfusion Microglial depletion (PLX5622, CSF1R inhibitor)

Cannula implantation, osmotic pump infusion, IP injection, blood collection and serum fractionation, brain microdissection, anesthesia (isoflurane, pentobarbital).

Behavioral phenotyping

Open field · MWM · EPM · NOR · SOR · Y-maze · Hindlimb clasp  ·  EthoVision XT, ANY-maze, HK MotorMonitor.

Histology & Tissue Processing

IHC (DAB · IF) Multi-label co-staining DiI neuronal tracing

Tissue sectioning (vibratome, microtome, cryostat); Nissl staining; antigen retrieval (heat-induced/citrate, formic acid, enzymatic/trypsin).

Microscopy, Stereology & Image Analysis

Confocal (Nikon A1R) ZEISS Axio Scan.Z1 ZEISS Axio Imager M1 Unbiased stereology Neurolucida

Widefield imaging (brightfield and fluorescence); whole-slide digital scanning; MBF Stereo Investigator (Optical Fractionator, Area Fraction Fractionator, Cavalieri); dendritic morphometry and 3D reconstruction (GFP-labeled neurons); image analysis (ImageJ/Fiji, NearCYTE).

Molecular Biology & Cell Culture

PCR / qRT-PCR Western blot ELISA Primary cell culture FACS

PCR (nested, multiplex; primer design); qRT-PCR (multiplex TaqMan); ELISA (sandwich); primary culture (NSCs, MSCs, microglia, neurons) and established lines (U87 glioblastoma); ICC; dose-response, proliferation, migration, and wound healing assays; cell passaging and cryopreservation; C. elegans (forward genetic screens, PCR, RNAi).

Biostatistics & Computation

R programming Non-parametric methods Effect size reporting Bootstrapped CIs

GraphPad Prism; SPSS; GitHub Pages. Statistical tests: Mann-Whitney U, Brunner-Munzel, ART ANOVA, permutation tests, Spearman correlation; Assumption testing: normality (Shapiro-Wilk, Anderson-Darling), heteroscedasticity (Levene's, Brown-Forsythe); Effect sizes (bootstrapped): Cliff's Delta, Hodges-Lehmann, Probability Index, Partial Eta/Omega Squared; Post-hoc: Holm-corrected contrasts; data visualization.

Credentials & Documents

CV & Documents

Curriculum Vitae

Full CV including research and professional experience, publications, conference presentations, teaching, and technical skills.

Download CV (PDF)

Awards & Grants

Teaching

Stress (PSY 459)

Instructor of record · CMU Department of Psychology · 2018

Syllabus SOS Scores

Research Methods (PSY 285) · Online

Instructor of record · CMU Department of Psychology · 2018

Syllabus SOS Scores

Professional Service

Get in Touch

Contact

Email
keenejosh22@gmail.com
Phone
(810) 287-5699
Location
Flint/Lansing, MI
ORCID iD
0009-0006-5104-2480
LinkedIn
linkedin.com/in/keenejosh