Background: Microdose lithium is protective against Alzheimer’s disease (AD), although the precise mechanisms through which its protective effects are conferred remain unclear. Objective: To further examine the effects during the earliest stages of Aβ pathology, we evaluated whether NP03, a microdose lithium formulation, modulates Aβ-mediated oxidative damage and neuroinflammation when applied to a rat transgenic model of AD-like amyloidosis overexpressing amyloid precursor protein (APP). Method: McGill-R-Thy1-APP transgenic rats and wild-type littermates were treated with NP03 or vehicle formulation for 8 weeks beginning at 3 months of age-a phase preceding Aβ plaque deposition in the transgenic rats. Results: Oxidative and nitrosative stress markers, protein-bound 4-hydroxynonenal (HNE) and protein-resident 3-nitrotyrosine (3-NT), inflammatory cytokines production, as well as microglial recruitment towards Aβ-burdened neurons were assayed. NP03 significantly decreased cerebral HNE and 3-NT, and reduced production of pro-inflammatory cytokines in McGill-R-Thy1-APP transgenic rats. NP03 further reduced expression of microglia surface receptor Trem2 and led to a corresponding reduction in microglia recruitment towards Aβ-burdened neurons in the CA1 region of the hippocampus. Conclusion: These results suggest that NP03 may function to slow the AD-like pathology in part by modifying oxidative/nitrosative damage and neuroinflammation, raising the possibility that low doses of microencapsulated lithium might be of therapeutic-preventive value during very early or preclinical AD.
|Number of pages||11|
|Journal||Current Alzheimer Research|
|State||Published - 2018|
Bibliographical noteFunding Information:
This work was supported by grants from the Canadian Institutes of Health Research (grant number 102752). SDC is the holder of the Charles E. Frosst/Merck Research Associate position. MFI was the recipient of a Biomedical Doctoral Award from the Alzheimer Society of Canada. HH is the holder of a Fonds de la Recherche en Santé Québec Postdoctoral Fellowship. ACC is the holder of the Charles E. Frosst/Merck-endowed Chair in Pharmacology and is a Team Leader for the Canadian Consortium on Neurodegeneration in Aging. We wish to thank Dr. Alan Frosst, the Frosst family, and Merck Canada for their continuing support.
© 2018 Bentham Science Publishers.
- Alzheimer’s disease
- Microdose lithium
- Oxidative stress
ASJC Scopus subject areas
- Clinical Neurology