Neurobiology of Disease. Volume 127, July 2019, Pages 432-448
B. Teter, T. Morihara, G.P. Lim, T. Chu, M.R. Jones, X. Zuo, R.M., Paul, S.A. Frautschy, G.M. Cole
Their work seems to have been done in a live mouse model and with human & mouse microglial cells in vitro. It's not clear to me what implications their dosing may have for those of us taking curcumin capsules.
They go into significant detail regarding the process by which they believe curcumin helps Aβ clearance. If you're interested in that level of detail and can get access to the paper, you may find it worthwhile.
- Curcumin (Curc) restores innate immune gene expression in AD models.
- Curc increased TREM2 and TYROBP, while decreasing CD33 expression.
- Curc stimulates phagocytosis and increases CD68 and Arg1 expression.
- Curc reduces pro-inflammatory microglia markers CD11b, iNOS, COX-2, IL1β.
- These results support a novel mechanism for Curc, which emulates the Aβ vaccine.
Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial phagocytosis of amyloid (Aβ). We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 [amounts] (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1β).
In contrast, very high dose curcumin did not show these effects, failed to clear amyloid plaques, and dysregulated gene expression relationships.
Curc-lo stimulated microglial migration to and phagocytosis of amyloid plaques both in vivo and in ex vivo assays of sections of human AD brain and of mouse brain. Curcumin also reduced levels of miR-155, a micro-RNA reported to drive a neurodegenerative microglial phenotype. In conditions without amyloid (human microglial cells in vitro, aged wild-type mice), Curc-lo similarly decreased CD33 and increased TREM2.
Like curcumin, anti-Aβ antibody (also reported to engage the Syk pathway, increase CD68, and decrease amyloid burden in human and mouse brain) increased TREM2 in APPsw mice and decreased amyloid in human AD sections ex vivo.
We conclude that curcumin is an immunomodulatory treatment capable of emulating anti-Aβ vaccine in stimulating phagocytic clearance of amyloid by reducing CD33 and increasing TREM2 and TyroBP, while restoring neuroinflammatory networks implicated in neurodegenerative diseases.
from the body of the paper, regarding dosage:
The effects of different doses of diet-administered curcumin, low dose (160 ppm, “Curc-Lo”) and 30-fold higher dose (5,000 ppm, “Curc-Hi”), on microglial activation and [amount] of AD genetic risk factor microglial genes were evaluated in APPSwe (Tg2576) transgenic amyloid plaque-forming mice. Tg2576 mice were fed curcumin doses of 0, 160 or 5,000 ppm in PMI 5015 breeder chow from 10 to 16 months of age.
We previously reported that these Curc-Lo-treated mice showed decreased inflammation and oxidative damage (e.g. decreased IL1β, GFAP and carbonyl (oxidized) proteins) as well as decreased Aβ levels (decreased amyloid plaque burden, soluble Aβ, and insoluble Aβ) in the brain (Lim et al., 2001). While using an intermediate dosing with 500 ppm from 17 to 22 months (after amyloid accumulation) produced large decreases in IL1β and amyloid burden (Yang et al., 2005), surprisingly, Curc-Hi did not affect insoluble or soluble Aβ levels (Lim et al., 2001),