Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer's Disease is Affected by A beta-ImmunoTherapy and Cognitive Stimulation

Alejandro R. Roda, Sandra Villegas*, Gisela Esquerda-Canals, Joaquim Martí-Clúa

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Clinical symptoms of Alzheimer’s Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2.5 months old and cognitive impairment in between 3-and 5-month-old mice. In this work, the effect of chronic Aβ-immunotherapy on behavioral and cognitive abilities was tested by monthly administering the antibody fragment scFv-h3D6 to 3xTg-AD female mice from 5 to 9 months of age. An untreated group was used as a reference, as well as to attain some information on the effect of training during the longitudinal study. Behavioral and psychological symptoms of dementia (BPSD)-like symptoms were already evident in 5-month-old mice, in the form of neophobia and anxious-like behavior. The exploratory activity decreased over the longitudinal study, not only for 3xTgAD mice but also for the corresponding non-transgenic mice (NTg). Learning abilities of 3xTg-AD mice were not seriously compromised but an impairment in long-term spatial memory was evident at 5 months of age. Interestingly, scFv-h3D6-treatment affected the cognitive impairment displayed by 5-month-old 3xTg-AD mice. It is worth noting that training also reduced cognitive impairment of 3xTg-AD mice over the longitudinal study, suggesting that to properly quantify the isolated therapeutic potential of any drug on cognition using this model it is convenient to perform a prompt, age-matched study rather than a longitudinal study. In addition, a combination of both training and Aβ-immunotherapy could constitute a possible approach to treat Alzheimer’s disease.

Original languageAmerican English
Article number944
Pages (from-to)1-21
Number of pages21
JournalPharmaceutics
Volume12
Issue number10
DOIs
Publication statusPublished - 2 Oct 2020

Keywords

  • 3xTg-AD
  • Alzheimer
  • Immunotherapy
  • ScFv
  • Tau
  • Training
  • DEMENTIA
  • tau
  • SYMPTOMS
  • TRIPLE-TRANSGENIC MODEL
  • training
  • A&#946
  • NATIONAL INSTITUTE
  • scFv
  • AMYLOID-BETA
  • HYPOTHESIS
  • PROGRESS
  • immunotherapy
  • MICE
  • DYSFUNCTION
  • INTERVENTION

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