6533b852fe1ef96bd12aa3c2
RESEARCH PRODUCT
Naturally occurring autoantibodies interfere with β-amyloid metabolism and improve cognition in a transgenic mouse model of Alzheimer's disease 24 h after single treatment
David MengelRichard DodelMichael BacherMaike GoldOliver DeusterOliver DeusterKarthikeyan BalakrishnanStephan RöskamJan-philipp BachFrauke NeffWolfgang H. Oertelsubject
Genetically modified mousemedicine.medical_specialtytoxic oligomersAmyloidBlotting WesternEnzyme-Linked Immunosorbent AssayMice TransgenicBiologyAnimals Genetically ModifiedCellular and Molecular NeuroscienceMiceCognitionAlzheimer DiseaseInternal medicinemedicineAnimalsBiological PsychiatryAutoantibodiesAmyloid beta-Peptidesβ-amyloidbehaviorAutoantibodyAlzheimer's diseasemedicine.diseasenatural occurring autoantibodiesCell biologyPsychiatry and Mental healthDisease Models AnimalEndocrinologyinflammationSynaptic plasticityToxicitybiology.proteinCytokinesCytokine secretionOriginal ArticleFemaleAlzheimer's diseaseAntibodydescription
There is evidence that naturally occurring antibodies directed against Aβ (nAbs-Aβ) have a role in Aβ-metabolism and Aβ-clearance. The presence of nAbs-Aβ leads to a reduction in amyloid fibrillation and thus a reduction in their toxicity. We investigated the effects of nAbs-Aβ in respect to oligomerization and used the Tg2576 transgenic mouse model in order to investigate the rapid effect with a single-dose (24 h) on oligomer breakdown and cytokine secretion along with immunohistochemical characterization of synaptic plasticity. nAbs-Aβ were able to reduce toxic oligomer concentration with an increase in Aβ-monomers. Cytokine secretion was significantly reduced. Synaptic plasticity was also improved after administration of nAbs. Finally, single treatment lead to a significant improvement in cognition. This study demonstrates the efficacy of nAbs-Aβ and presents evidence that several hallmarks of the disease are targeted by nAbs-Aβ.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-03-01 | Translational Psychiatry |