Non-invasive　phototherapy　has　been　emerging　as　an　ambitious　tactic　for　suppression　of　amyloid-β　(Aβ)　self-assembly　against　Alzheimer＇s　disease　(AD).　However,　it　remains　a　daunting　challenge　to　develop　efficient　photosensitizers　for　Aβ　oxygenation　that　are　activatable　in　a　deep　brain　tissue　through　the　scalp　and　skull,　while　reducing　side　effects　on　normal　tissues.　Here,　we　report　an　Aβ　targeted,　low-dose　X-ray-excitable　long-afterglow　scintillator　(ScNPs@RB/Ab)　for　efficient　deep-brain　phototherapy.　We　demonstrate　that　the　as-synthesized　ScNPs@RB/Ab　is　capable　of　converting　X-rays　into　visible　light　to　activate　the　photosensitizers　of　rose　bengal　(RB)　for　Aβ　oxygenation　through　the　scalp　and　skull.　We　show　that　the　ScNPs@RB/Ab　persistently　emitting　visible　luminescence　can　substantially　minimize　the　risk　of　excessive　X-ray　exposure　dosage.　Importantly,　peptide　KLVFFAED-functionalized　ScNPs@RB/Ab　shows　a　blood–brain　barrier　permeability.　In　vivo　experimental　results　validated　that　ScNPs@RB/Ab　alleviated　Aβ　burden　and　slowed　cognitive　decline　in　triple-transgenic　AD　model　mice　at　extremely　low　X-ray　doses　without　side　effects.　Our　study　paves　a　new　pathway　to　develop　high-efficiency　transcranial　AD　phototherapy.　Statement　of　significance:　Non-invasive　phototherapy　has　been　emerging　as　an　ambitious　tactic　for　suppression　of　amyloid-β　(Aβ)　self-assembly　against　Alzheimer＇s　disease　(AD).　However,　it　remains　a　daunting　challenge　to　develop　efficient　photosensitizers　for　Aβ　oxygenation　that　are　activatable　in　a　deep　brain　tissue　through　the　scalp　and　skull,　while　reducing　side　effects　on　normal　tissues.　Herein,　we　report　an　Aβ　targeted,　low-dose　X-ray-excitable　long-afterglow　scintillators　(ScNPs@RB/Ab)　for　efficient　deep-brain　phototherapy.　In　vivo　experimental　results　validated　that　ScNPs@RB/Ab　alleviated　Aβ　burden　and　slowed　cognitive　decline　in　triple-transgenic　AD　model　mice　at　extremely　low　X-ray　doses　without　side　effects.　©　2022　Acta　Materialia　Inc.