# Gary E. Landreth
**Gary E. Landreth** is an American neuroscientist, the Martin Professor of Alzheimer's Research and a professor of anatomy, cell biology, and physiology at the [Indiana University School of Medicine](https://www.edgepedia.org/indiana-university-school-of-medicine)'s Stark Neurosciences Research Institute, where he also serves as executive associate director of education.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) He directed the Alzheimer Research Laboratory at [Case Western Reserve University](https://www.edgepedia.org/case-western-reserve-university) for 27 years, from 1989 until 2016, before moving to Indiana.[2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) His research centers on the principal genetic risk factors for Alzheimer's disease: the biology of apolipoprotein E (apoE), inflammatory mechanisms, and the microglia genes TREM2 and [PLCG2](https://www.edgepedia.org/plcg2).[1](https://medicine.iu.edu/faculty/27243/landreth-gary) He is known for a 2012 *Science* study showing that the drug bexarotene rapidly cleared β-amyloid and reversed deficits in Alzheimer's mouse models, and for work tracing how genetic variants of the microglial enzyme phospholipase C-γ2 (PLCG2) change disease risk.[3](https://www.science.org/doi/10.1126/science.1217697)
| Key facts | |
|---|---|
| Current position | Martin Professor of Alzheimer's Research; professor of anatomy, cell biology & physiology; executive associate director of education, Stark Neurosciences Research Institute, Indiana University School of Medicine (since 2017)[1](https://medicine.iu.edu/faculty/27243/landreth-gary) • [2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) |
| Training | BS in Chemistry and Biochemistry, University of Kansas, 1972; PhD, Neuroscience Graduate Program, University of Michigan, 1977 (its first PhD graduate); postdoc at Stanford with Eric Shooter[1](https://medicine.iu.edu/faculty/27243/landreth-gary) • [2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) |
| Earlier career | Medical University of South Carolina faculty, 1980–1989; Case Western Reserve University, 1989–2016, directing the Alzheimer Research Laboratory[1](https://medicine.iu.edu/faculty/27243/landreth-gary) |
| Signature work | ApoE-directed therapeutics clearing β-amyloid in AD mouse models, *Science*, 2012[3](https://www.science.org/doi/10.1126/science.1217697) |
| Microglia genetics | PLCG2 P522R attenuates and M28L exacerbates disease in amyloidogenic AD mice, *Immunity*, 2023[4](https://doi.org/10.1016/j.immuni.2023.08.008) |
| Industry role | Co-founder of ReXceptor, Inc., which received an exclusive license from Case Western Reserve for the bexarotene strategy[5](https://www.eurekalert.org/news-releases/777672) |
| Status | Planning retirement from Indiana after nearly 50 years of research; honored by an October 9 symposium from colleagues and trainees[2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) |
## Education and career
Landreth received his undergraduate degree in Chemistry and [Biochemistry](https://www.edgepedia.org/biochemistry) from the [University of Kansas](https://www.edgepedia.org/university-of-kansas) in 1972.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) He completed a PhD in the Neuroscience Program at the University of Michigan in 1977, including a year of study at the National Institute of Medical Research in London, and was the first student to graduate with a PhD from the university's Neuroscience Graduate Program.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) • [2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) He then carried out postdoctoral work in the Department of Neurobiology at Stanford with Eric Shooter, the department's founding chair.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) • [2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement)
In 1980 he was appointed to the faculty of the [Medical University of South Carolina](https://www.edgepedia.org/medical-university-of-south-carolina), where he worked for nine years.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) He moved in 1989 to the Department of Neurosciences at Case Western Reserve University, where, according to a CWRU Medical Breakthroughs profile, he was professor of neurosciences and neurology, director of the Alzheimer Research Laboratory until 2016, and director of graduate education for the department.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) • [6](https://case.edu/medbreakthroughs/about/landreth.html) In 2017 the executive director of the Stark Neurosciences Research Institute, who had come to the IU School of Medicine in 2016 from the [Cleveland Clinic](https://www.edgepedia.org/cleveland-clinic), recruited him to Indiana.[2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement) There, as executive associate director of education at Stark, he restructured the institute's Medical Neuroscience Graduate Program, created a new curriculum and expanded offerings for MD-PhD trainees.[2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement)
## Representative work
The 2012 *Science* paper ApoE-Directed Therapeutics Rapidly Clear β-[Amyloid](https://www.edgepedia.org/amyloid) and Reverse Deficits in AD Mouse Models ([3](https://www.science.org/doi/10.1126/science.1217697), published online 9 February 2012; print issue 23 March 2012) reported that oral administration of the retinoid X receptor (RXR) agonist bexarotene to an Alzheimer's mouse model enhanced clearance of soluble Aβ within hours in an apoE-dependent manner, reduced Aβ plaque area by more than 50% within 72 hours, and rapidly reversed cognitive, social, and olfactory deficits while improving neural circuit function.[3](https://www.science.org/doi/10.1126/science.1217697) The mechanism rests on apoE expression being transcriptionally induced by the nuclear receptors PPARγ and the liver X receptors in coordination with RXRs.[3](https://www.science.org/doi/10.1126/science.1217697) The result was covered widely in the lay media, including National Public Radio.[7](https://www.alzforum.org/news/research-news/upping-brain-apoe-drug-treats-alzheimers-mice)
The laboratory's later program turned to microglia, the brain's immune cells. Recent GWAS studies show that about 40% of all Alzheimer's disease risk genes are linked to the immune response mediated by microglia, and genetic variants of PLCG2 can confer both elevated risk for and protection from the disease.[1](https://medicine.iu.edu/faculty/27243/landreth-gary) A 2022 *Alzheimer's & Dementia* paper found that the P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's mouse model.[8](https://curealz.org/researchers/gary-landreth/) The 2023 *Immunity* study showed that PLCG2 P522R attenuated disease in an amyloidogenic murine AD model, whereas PLCG2 M28L exacerbated plaque burden with altered phagocytosis and Aβ clearance; the two variants bidirectionally modulated pathology by inducing distinct transcriptional programs that identified microglial subpopulations with protective or detrimental phenotypes.[4](https://doi.org/10.1016/j.immuni.2023.08.008)
## Industry and translation
According to SciBX coverage, bexarotene, trademarked as Targretin, is a drug the U.S. [Food and Drug Administration](https://www.edgepedia.org/food-and-drug-administration) had originally approved for cancer; it was chosen over LXR agonists, which have a poor side-effect profile, and over PPARγ agonists after rosiglitazone failed a Phase III Alzheimer's trial in 2009.[5](https://www.eurekalert.org/news-releases/777672) • [9](https://doi.org/10.1038/scibx.2012.221) In cultured microglia and astrocytes, the drug stimulated APOE expression, promoted degradation of soluble Aβ and increased secretion of HDL particles; earlier work from the laboratory had shown that an LXR agonist enhanced brain APOE levels, increasing both Aβ degradation and cognition in mice.[9](https://doi.org/10.1038/scibx.2012.221)
Landreth and his then-graduate student co-founded ReXceptor, Inc., after finding that a single dose of bexarotene reversed Alzheimer's symptoms in mice within 72 hours.[5](https://www.eurekalert.org/news-releases/777672) Case Western Reserve's Technology Transfer Office granted the company an exclusive license to the treatment strategy, with early-stage human clinical trials planned within months.[5](https://www.eurekalert.org/news-releases/777672) Landreth held a provisional patent application on bexarotene as a potential Alzheimer's therapeutic.[3](https://www.science.org/doi/10.1126/science.1217697) A double-blind, placebo-controlled proof-of-concept trial subsequently randomized twenty patients with moderate Alzheimer's disease (MMSE 10–20, positive florbetapir scans) to 300 mg of bexarotene or placebo for four weeks.[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC4731943/)
## Recent developments
The laboratory's recent output centers on the PLCG2 and TREM2 genetics of microglia, including the 2023 *Immunity* variant study.[4](https://doi.org/10.1016/j.immuni.2023.08.008) Landreth's work at Case Western Reserve was supported by the National Institute on Aging, including grant R01 AG016740 on microglial signaling mechanisms in Alzheimer's disease, with a reported annual amount of $268,538 in the 2009 record.[11](https://grantome.com/grant/NIH/R01-AG016740-08) After nearly 50 years leading neuroscience research and education programs, he is planning to retire from his Indiana post; colleagues and past trainees organized a symposium in his honor, "Beyond the Bench: Honoring Dr. Gary Landreth's Contributions to Science and Mentorship," on October 9 at the IU School of Medicine.[2](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement)
## References
1. [Gary E. Landreth, PhD, IU School of Medicine faculty profile](https://medicine.iu.edu/faculty/27243/landreth-gary)
2. [Alzheimer's disease researcher looks back at early days of neuroscience research, importance of mentoring as he nears retirement](https://medicine.iu.edu/blogs/neuroscience/Gary-Landreth-retirement)
3. [ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models (Science, 2012)](https://www.science.org/doi/10.1126/science.1217697)
4. [Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer's disease (Immunity, 2023)](https://doi.org/10.1016/j.immuni.2023.08.008)
5. [Research spinoff ReXceptor gets license for Alzheimer's treatment (EurekAlert/Case Western Reserve)](https://www.eurekalert.org/news-releases/777672)
6. [Medical Breakthroughs, Gary Landreth, Ph.D. (Case Western Reserve University)](https://case.edu/medbreakthroughs/about/landreth.html)
7. [Upping Brain ApoE, Drug Treats Alzheimer's Mice | ALZFORUM](https://www.alzforum.org/news/research-news/upping-brain-apoe-drug-treats-alzheimers-mice)
8. [Gary Landreth – Cure Alzheimer's Fund](https://curealz.org/researchers/gary-landreth/)
9. [APOE in AD (SciBX, Nature Biotechnology trade coverage)](https://doi.org/10.1038/scibx.2012.221)
10. [Double-blind, placebo-controlled, proof-of-concept trial of bexarotene in moderate Alzheimer's disease](https://pmc.ncbi.nlm.nih.gov/articles/PMC4731943/)
11. [Microglial Signaling Mechanisms in Alzheimer's Disease, NIH R01 AG016740-08](https://grantome.com/grant/NIH/R01-AG016740-08)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in neuroscience › Neurodegeneration and disease models*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 15, 2026; Oct 21, 2026; Oct 25, 2026 · Last review: Sep 25, 2026*
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