CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease

Antonella Caccamo, Monica A. Maldonado, Alex F. Bokov, Smita Majumder, Salvatore - Oddo

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Cognitive dysfunction and memory loss are common features of Alzheimer's disease (AD). Abnormalities in the expression profile of immediate early genes that play a critical role in memory formation, such as the cAMP-response element binding protein (CREB), have been reported in the brains of AD patients. Here we show that amyloid-β (Aβ) accumulation, which plays a primary role in the cognitive deficits of AD, interferes with CREB activity. We further show that restoring CREB function via brain viral delivery of the CREB-binding protein (CBP) improves learning and memory deficits in an animal model of AD. Notably, such improvements occur without changes in Aβ and tau pathology, and instead are linked to an increased level of brain-derived neurotrophic factor. The resulting data suggest that Aβ-induced learning and memory deficits are mediated by alterations in CREB function, based on the finding that restoring CREB activity by directly modulating CBP levels in the brains of adult mice is sufficient to ameliorate learning and memory. Therefore, increasing CBP expression in adult brains may be a valid therapeutic approach not only for AD, but also for various brain disorders characterized by alterations in immediate early genes, further supporting the concept that viral vector delivery may be a viable therapeutic approach in neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)22687-22692
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number52
DOIs
StatePublished - Dec 28 2010
Externally publishedYes

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CREB-Binding Protein
Cyclic AMP Response Element-Binding Protein
Brain-Derived Neurotrophic Factor
Memory Disorders
Alzheimer Disease
Learning
Genes
Immediate-Early Genes
Brain Diseases
Brain
Amyloid
Protein Binding
Neurodegenerative Diseases
Transfer (Psychology)
Carrier Proteins
Animal Models
Pathology
Therapeutics

Keywords

  • Presenilin
  • Tangles

ASJC Scopus subject areas

  • General

Cite this

CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease. / Caccamo, Antonella; Maldonado, Monica A.; Bokov, Alex F.; Majumder, Smita; Oddo, Salvatore -.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 52, 28.12.2010, p. 22687-22692.

Research output: Contribution to journalArticle

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