Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease

CHEN Yanqing; GONG Ping; LIU Zhen; ZHANG Yan; YU Yang

doi:10.11665/j.issn.1000-5048.20210511

Journal of China Pharmaceutical University > 2021 > 52(5): 586-595. > DOI: 10.11665/j.issn.1000-5048.20210511

CHEN Yanqing, GONG Ping, LIU Zhen, ZHANG Yan, YU Yang. Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease[J]. Journal of China Pharmaceutical University, 2021, 52(5): 586-595. DOI: 10.11665/j.issn.1000-5048.20210511

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Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 81870835, No.81571027)

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Received Date: February 03, 2021
Revised Date: September 11, 2021

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Abstract

Abstract

To explore the effects of serum amyloid A (SAA) on the cognitive function and tau phosphorylation in Alzheimer''s disease (AD), two mouse models of AD were constructed: one is the APP/PS1 double transgenic mice mated with the Saa3 knockout (Saa3^-/-) mice, and the other involves intracerebroventricular (ICV) injection of streptozotocin (STZ) into WT and Saa3^-/- mice.The expression of Saa3 in mouse brain was evaluated using immunofluorescence staining.The body weight of STZ injection mice during modeling was measured.The motor coordination and balance, spontaneous exploratory activity, and anxiety level of these mice were assessed by Rotarod test, open field, and elevated plus maze, respectively.Spatial reference learning and memory were evaluated by Morris water maze.Western blot was used to detect the phosphorylation level of tau protein in mouse brain tissue.The results showed that the expression of Saa3 was increased in the brain of AD mice.The Saa3 gene deletion had no significant effect on motor coordination, balance and spontaneous exploratory activity in these mice, yet with alleviated anxiety level of AD model mice.Saa3 deficiency improved the impairment of learning and memory function of intracerebroventricular STZ injection mice and APP/PS1 mice. Deletion of Saa3 relieved the hyperphosphorylation of tau protein at specific sites in the brain of AD mice. The difference between the groups was statistically significant (P < 0.05). These results suggest that Saa3 is associated with cognitive function and tau pathology in AD, and that the inhibition of SAA may be a new strategy for the treatment of AD.
- serum amyloid A,
- Alzheimer''s Disease,
- Tau phosphorylation,
- Morris water maze

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References

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