Intraneuronal Aβ causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice

Lauren M. Billings, Salvatore Oddo, Kim N. Green, James L. McGaugh, Frank M. LaFerla

Research output: Contribution to journalArticle

865 Citations (Scopus)

Abstract

Progressive memory loss and cognitive dysfunction are the hallmark clinical features of Alzheimer's disease (AD). Identifying the molecular triggers for the onset of AD-related cognitive decline presently requires the use of suitable animal models, such as the 3xTg-AD mice, which develop both amyloid and tangle pathology. Here, we characterize the onset of learning and memory deficits in this model. We report that 2-month-old, prepathologic mice are cognitively unimpaired. The earliest cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala. Plaque or tangle pathology is not apparent at this age, suggesting that they contribute to cognitive dysfunction at later time points. Clearance of the intraneuronal Aβ pathology by immunotherapy rescues the early cognitive deficits on a hippocampal-dependent task. Reemergence of the Aβ pathology again leads to cognitive deficits. This study strongly implicates intraneuronal Aβ in the onset of cognitive dysfunction.

Original languageEnglish (US)
Pages (from-to)675-688
Number of pages14
JournalNeuron
Volume45
Issue number5
DOIs
StatePublished - Mar 3 2005
Externally publishedYes

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Transgenic Mice
Alzheimer Disease
Pathology
Memory Disorders
Amygdala
Amyloid
Immunotherapy
Hippocampus
Animal Models
Cognitive Dysfunction
Learning

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Intraneuronal Aβ causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. / Billings, Lauren M.; Oddo, Salvatore; Green, Kim N.; McGaugh, James L.; LaFerla, Frank M.

In: Neuron, Vol. 45, No. 5, 03.03.2005, p. 675-688.

Research output: Contribution to journalArticle

Billings, Lauren M. ; Oddo, Salvatore ; Green, Kim N. ; McGaugh, James L. ; LaFerla, Frank M. / Intraneuronal Aβ causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. In: Neuron. 2005 ; Vol. 45, No. 5. pp. 675-688.
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