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. 2024 Sep 10;230(Supplement_2):S165-S172.
doi: 10.1093/infdis/jiae227.

Toxoplasma gondii Infection of Alzheimer's Disease Mice Reduces Brain Amyloid Density Globally and Regionally

Katherine J O Yanes  1   2 , Nathanial A Guanzon  3 , Ricardo Azevedo  3 , Damian G Wheeler  3 , Sunil P Gandhi  3 , Melissa B Lodoen  1   2
Affiliations

Toxoplasma gondii Infection of Alzheimer's Disease Mice Reduces Brain Amyloid Density Globally and Regionally

Katherine J O Yanes et al. J Infect Dis. .

Abstract

Background: Toxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid β plaques. We aimed to determine if there is a brain regional difference in amyloid β reduction in the brains of T. gondii-infected compared to control mice.

Method: Three-month-old 5xFAD (AD model) mice were injected with T. gondii or with phosphate-buffered saline as a control. Intact brains were harvested at 6 weeks postinfection, optically cleared using iDISCO+, and brain-wide amyloid burden was visualized using volumetric light-sheet imaging. Amyloid signal was quantified across each brain and computationally mapped to the Allen Institute Brain Reference Atlas to determine amyloid density in each region.

Results: A brain-wide analysis of amyloid in control and T. gondii-infected 5xFAD mice revealed that T. gondii infection decreased amyloid burden in the brain globally as well as in the cortex and hippocampus, and many daughter regions. Daughter regions that showed reduced amyloid burden included the prelimbic cortex, visual cortex, and retrosplenial cortex. The olfactory tubercle, a region known to have increased monocytes following T. gondii infection, also showed reduced amyloid after infection.

Conclusions: T. gondii infection of AD mice reduces amyloid burden in a brain region-specific manner that overlaps with known regions of T. gondii infection and peripheral immune cell infiltration.

Keywords: Toxoplasma gondii; 5xFAD; Alzheimer's disease; amyloid β; brain; iDISCO+; light-sheet imaging; neuroinfection.

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References

    1. Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol 2020; 17:157–72. - PubMed
    1. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 2016; 8:595–608. - PMC - PubMed
    1. Zhang Y, Chen H, Li R, Sterling K, Song W. Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future. Signal Transduct Target Ther 2023; 8:1–26. - PMC - PubMed
    1. Arboleda-Velasquez JF, Lopera F, O’Hare M, et al. . Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019; 25:1680–3. - PMC - PubMed
    1. Itzhaki RF. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts. FASEB J 2017; 31:3216–26. - PubMed

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