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, Salvatore Oddo, A. Tobeña, F. M. LaFerla, A. Fernández-Teruel

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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
Volume31
Issue number1
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

Behavioral Symptoms
Amyloid
Alzheimer Disease
Cholinergic Agents
Technology Transfer
Amyloid Plaques
Brain
Down Syndrome
Transgenes
Cell Death
Animal Models
Biomarkers
Research
Genes

Keywords

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

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice : A role for intraneuronal amyloid. / Giménez-Llort, L.; Blázquez, G.; Cañete, T.; Johansson, B.; Oddo, Salvatore; Tobeña, A.; LaFerla, F. M.; Fernández-Teruel, A.

In: Neuroscience and Biobehavioral Reviews, Vol. 31, No. 1, 2007, p. 125-147.

Research output: Contribution to journalArticle

Giménez-Llort, L, Blázquez, G, Cañete, T, Johansson, B, Oddo, S, Tobeña, A, LaFerla, FM & Fernández-Teruel, A 2007, 'Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: A role for intraneuronal amyloid', Neuroscience and Biobehavioral Reviews, vol. 31, no. 1, pp. 125-147. https://doi.org/10.1016/j.neubiorev.2006.07.007
Giménez-Llort, L. ; Blázquez, G. ; Cañete, T. ; Johansson, B. ; Oddo, Salvatore ; Tobeña, A. ; LaFerla, F. M. ; Fernández-Teruel, A. / Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice : A role for intraneuronal amyloid. In: Neuroscience and Biobehavioral Reviews. 2007 ; Vol. 31, No. 1. pp. 125-147.
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