Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: A role for intraneuronal amyloid

L. Giménez-Llort, G. Blázquez, T. Cañete, B. Johansson, S. Oddo, A. Tobeña, F. M. LaFerla, A. Fernández-Teruel

Research output: Contribution to journalReview articlepeer-review

198 Scopus citations


The amyloid Aβ-peptide (Aβ) is suspected to play a critical role in the cascade leading to AD as the pathogen that causes neuronal and synaptic dysfunction and, eventually, cell death. Therefore, it has been the subject of a huge number of clinical and basic research studies on this disease. Aβ is typically found aggregated in extracellular amyloid plaques that occur in specific brain regions enriched in nAChRs in Alzheimer's disease (AD) and Down syndrome (DS) brains. Advances in the genetics of its familiar and sporadic forms, together with those in gene transfer technology, have provided valuable animal models that complement the traditional cholinergic approaches, although modeling the neuronal and behavioral deficits of AD in these models has been challenging. More recently, emerging evidence indicates that intraneuronal accumulation of Aβ may also contribute to the cascade of neurodegenerative events and strongly suggest that it is an early, pathological biomarker for the onset of AD and associated cognitive and other behavioral deficits. The present review covers these studies in humans, in in vitro and in transgenic models, also providing more evidence that adult 3×Tg-AD mice harboring PS1M146V, APPSwe, tauP301L transgenes, and mimicking many critical hallmarks of AD, show cognitive deficits and other behavioral alterations at ages when overt neuropathology is not yet observed, but when intraneuronal Aβ, synaptic and cholinergic deficits can already be described.

Original languageEnglish (US)
Pages (from-to)125-147
Number of pages23
JournalNeuroscience and Biobehavioral Reviews
Issue number1
StatePublished - 2007


  • 3xTgAD mice
  • Activity
  • Animal models
  • Circadian rhythms
  • Emotion
  • Intraneuronal amyloid
  • Learning and memory
  • Neuropsychiatric-like symptoms
  • Psychosis

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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