Locus coeruleus degeneration impairs forebrain arteriole physiology and perfusion in a rat model of Alzheimer's disease
The locus coeruleus (LC) provides forebrain norepinephrine (NE) and degenerates early in Alzheimer's disease (AD). We have shown that experimental LC lesions in the Tg344-19 AD rat model result in parenchymal arteriole (PA) stenosis, blood-brain barrier permeability, amyloid angiopathy, and cognitive impairment. Here, we show that PAs from LC-lesioned Tg344-19 AD rats displayed increased myogenic tone and decreased responsiveness to TRPV4 channel agonists, which was reversible by NE replacement. MRI studies indicated reduced forebrain perfusion and fractional anisotropy in LC-lesioned animals compared to controls. Targeting LC-mediated effects on cerebral hemodynamics presents a compelling AD therapeutic target.
Authors
- Laura C. Chambers (ORCID: https://orcid.org/0000-0002-3836-8703)
- Robert W. Wiseman (ORCID: https://orcid.org/0000-0003-1832-7805)
- John S. Beck (ORCID: https://orcid.org/0000-0003-4063-4422)
- Mahsa Gifani (ORCID: https://orcid.org/0000-0002-0645-2927)
- Zachary J. Fernandez (ORCID: https://orcid.org/0000-0001-6874-2252)
- Anne McLaren Dorrance (ORCID: https://orcid.org/0000-0001-6573-2729)
- Scott Counts (ORCID: https://orcid.org/0000-0003-2851-9763)
- Chunqi Qian (ORCID: https://orcid.org/0000-0003-4528-4572)
Institutions
- Michigan State University (US)
Publication Details
- Journal
- Journal of Alzheimer s Disease
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1177/13872877261496548
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute on Aging