Objective:　The　impairment　of　cognitive　function　has　been　associated　with　Alzheimer＇s　disease　(AD).　Exercise　exerts　a　positive　modulatory　effect　on　cognition　by　reducing　synapse　injury.　However,　limited　in　vivo　evidence　is　available　to　validate　the　neuroprotective　effect　of　TREM2　on　synaptic　function　in　this　phenomenon.　Here,　we　aim　to　explore　whether　physical　exercise　pretreatment　alters　Aβ-induced　recognition　memory　impairment　in　structural　synaptic　plasticity　within　the　hippocampus　in　AD　rats.　Methods：:　In　study　1,　fifty-two　Sprague-Dawley　(SD)　rats　were　randomly　divided　into　following　four　groups:　control　group　(C　group,　n　=　13),　Alzheimer＇s　disease　group　(AD　group,　n　=　13),　4　weeks　of　physical　exercise　and　Alzheimer＇s　disease　group　(Exe+AD　group,　n　=　13),　4　weeks　of　physical　exercise　and　blank　group　(Exercise　group,　n　=　13).　Four　weeks　of　treadmill　exercise　intervention　was　performed,　and　AD　model　were　established　by　intra-cerebroventricular　injection　(ICV)　injection　of　Aβ1–42　protein.　After　3　weeks,　we　also　conducted　a　novel　object　test　to　evaluate　recognition　memory　in　the　behavior　assessment.　Golgi　staining　and　transmission　electron　microscopy　were　used　to　evaluate　the　morphology　and　synaptic　ultrastructure　of　neurons.　Western　blotting　was　used　to　measure　the　expression　of　hippocampal　synaptic　proteins.　Extracellular　neurotransmitters　in　the　hippocampus　were　detected　by　microdialysis　coupled　with　high-performance　liquid　chromatography.　In　study　2,　33　SD　rats　were　randomly　divided　into　three　groups:　4　weeks　of　physical　exercise　and　Alzheimer＇s　disease　group　(Exe+AD　group,　n　=　11),　AAV-Control　and　physical　exercise　and　Alzheimer＇s　disease　group　(AAV-Control+Exe+AD　group,　n　=　11),　AAV-TREM2　and　physical　exercise　and　Alzheimer＇s　disease　group　(AAV-TREM2　+Exe+AD　group,　n　=　11).　Stereotactic　intracerebral　injection　in　the　bilateral　hippocampus　was　performed　to　achieve　microglial　TREM2　down-expression　by　using　adeno-associated　virus　(AAV)　with　CD68　promoter.　After　4　weeks　treadmill　exercise　and　3　weeks　Aβ　injection,　all　rats　received　behavior　test　and　molecular　experiment,　which　the　same　with　experiment　2.　Results:　Novel　recognition　index　in　novel　object　recognition　test　significantly　decreased,　and　western　blot　demonstrate　that　hippocampal　TREM2　protein　is　significantly　decreased　(P　＜　0.001).　But　physical　exercise　reversed　this　phenomenon(P　＜　0.001).　In　addition,　compared　with　Con　group,　the　neuron　from　Exe+AD　group　exhibited　a　more　complex　branching　pattern　(P　＜　0.05).　And　impaired　synaptic　ultrastructure　was　observed　in　AD　group.　Hippocampal　synaptic-related　protein　(SYX,　SYP,　GAP43,　PSD95)　and　neurotransmitter　(DA,　Glu,　GABA)　was　also　significantly　decreased　(P　＜　0.01)　in　AD　group.　But　the　neuroprotection　effect　can　be　found　in　Exe+AD　group,　which　are　associated　with　the　inhibition　of　synaptic　injury　by　activate　hippocampal　TREM2　(P　＜　0.05).　However,　when　blockade　of　hippocampal　TREM2　reduced　brain　protective　effect　of　exercise　in　AD　rat　model,　including　increased　the　damage　of　neuronal　dendritic　complexity,　synaptic　ultrastructure,　and　the　decrease　of　hippocampal　synapses-related　protein,　typical　neurotransmitter.　Conclusion:　Treadmill　exercise　facilitated　recognition　memory　acquisition　via　TREM2-mediated　structural　synaptic　plasticity　of　the　hippocampus　in　an　AD　rat　model.　©　2025　The　Authors