title: Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer's disease.
abstract: BACKGROUND
  The progressive development of Alzheimer's disease (AD) pathology follows a spatiotemporal pattern in the human brain. In a transgenic (Tg) mouse model of AD expressing amyloid precursor protein (APP) with the arctic (E693G) mutation, pathology spreads along anatomically connected structures. Amyloid-β (Aβ) pathology first appears in the subiculum and is later detected in interconnected brain regions, including the retrosplenial cortex. We investigated whether the spatiotemporal pattern of Aβ pathology in the Tg APP arctic mice to interconnected brain structures can be interrupted by destroying neurons using a neurotoxin and thereby disconnecting the neural circuitry.
  
  
  RESULTS
  We performed partial unilateral ibotenic acid lesions of the subiculum (first structure affected by Aβ pathology) in young Tg APParc mice, prior to the onset of pathology. We assessed Aβ/C99 pathology in mice aged up to 6 months after injecting ibotenate into the subiculum. Compared to the brains of intact Tg APP arctic mice, we observed significantly decreased Aβ/C99 pathology in the ipsilateral dorsal subiculum, CA1 region of the hippocampus and the retrosplenial cortex; regions connecting to and from the dorsal subiculum. By contrast, Aβ/C99 pathology was unchanged in the contralateral hippocampus in the mice with lesions.
  
  
  CONCLUSIONS
  These results, obtained in an animal model of AD, support the notion that Aβ/C99 pathology is transmitted between interconnected neurons in AD.
authors: Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden. sonia.george@vai.org.
authors: Sonia
authors: S
authors: George
authors: Annica
authors: A
authors: Rönnbäck
authors: Gunnar K
authors: GK
authors: Gouras
authors: Géraldine H
authors: GH
authors: Petit
authors: Fiona
authors: F
authors: Grueninger
authors: Bengt
authors: B
authors: Winblad
authors: Caroline
authors: C
authors: Graff
authors: Patrik
authors: P
authors: Brundin
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000293:injuries* / Q000502:physiology; D006801:Humans; D007051:Ibotenic Acid / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid