Transplantation of GABAergic Interneuron Progenitors Restores Cortical Circuit Function in an Alzheimer's Disease Mouse Model
In addition to dementia, Alzheimer's patients suffer from sleep impairments and aberrations in sleep-dependent brain rhythms. Deficits in inhibitory GABAergic interneuron function disrupt one of those rhythms, slow oscillation in particular, and actively contribute to Alzheimer's progression. The degree to which transplantation of healthy donor interneuron progenitors restores slow oscillation rhythm in young APP/PS1 mice is tested. Medial ganglionic eminence (MGE) progenitors are harvested from mouse embryos and transplanted them into host APP/PS1 mutant cortices. 3D light-sheet and structured illumination microscopy revealed that transplanted MGE progenitors survived and matured into healthy interneurons. In vivo multiphoton calcium imaging and voltage-sensitive dye imaging showed functional integration and slow oscillation rescue in the absence or presence of optogenetic stimulation. The work provides proof-of-concept evidence that stem cell therapy may serve as a viable strategy to rescue functional impairments in cortical circuits of APP/PS1 mice and potentially those of Alzheimer's patients.
Authors
- Heather M. Brown (ORCID: https://orcid.org/0000-0001-9636-2345)
- April M Stafford (ORCID: https://orcid.org/0000-0001-8312-4380)
- Theodore J. Zwang (ORCID: https://orcid.org/0000-0002-6815-4482)
- Megi Maci (ORCID: https://orcid.org/0000-0003-2907-0793)
- Daniel Vogt (ORCID: https://orcid.org/0000-0003-1876-5936)
- Ksenia V. Kastanenka (ORCID: https://orcid.org/0000-0002-3727-0317)
- Shinya Yokomizo (ORCID: https://orcid.org/0000-0003-4096-9695)
- Shinobu Inagaki (ORCID: https://orcid.org/0000-0002-2785-1214)
- Janice R. Naegele (ORCID: https://orcid.org/0000-0001-5151-0543)
- Rebecca L. Gillani (ORCID: https://orcid.org/0000-0002-4510-1740)
- Morgan R. Miller (ORCID: https://orcid.org/0000-0002-3740-8144)
- Douglas D. Richardson (ORCID: https://orcid.org/0000-0001-8488-6758)
- Stephen J. Perle (ORCID: https://orcid.org/0009-0003-9722-8131)
- Moustafa Algamal
- Liu-tao LIANG
- Shusaku Takahashi
- Alex Lovely
Institutions
- Wesleyan University (US)
- Grand Rapids Community College (US)
- Harvard University (US)
- Harvard University Press (US)
- MaineGeneral Medical Center (US)
- Michigan State University (US)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1002/advs.202511472
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- National Institutes of Health
- Japan Society for the Promotion of Science