Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice

Autor: Melissa Runfeldt, Huntington Potter, Malgorzata Mamcarz, Alexander Dickson, Kavon Rezai-Zadeh, Jun Tan, Chuanhai Cao, Takashi Mori, Bruce A. Citron, Xiaoyang Lin, Gary W. Arendash, Valentina Echeverria
Rok vydání: 2009
Předmět:
Genetically modified mouse
medicine.medical_specialty
Hippocampus
Enzyme-Linked Immunosorbent Assay
Mice
Transgenic
Hippocampal formation
Models
Biological
Presenilin
Gene Expression Regulation
Enzymologic
chemistry.chemical_compound
Amyloid beta-Protein Precursor
Glycogen Synthase Kinase 3
Mice
GSK-3
Alzheimer Disease
Internal medicine
Caffeine
mental disorders
medicine
Presenilin-1
Animals
Humans
Maze Learning
Cell Line
Transformed
Neurons
Amyloid beta-Peptides
business.industry
General Neuroscience
Age Factors
Brain
General Medicine
Entorhinal cortex
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Proto-Oncogene Proteins c-raf
Psychiatry and Mental health
Clinical Psychology
Disease Models
Animal
Endocrinology
chemistry
Central Nervous System Stimulants
Geriatrics and Gerontology
Alzheimer's disease
business
Cognition Disorders
Neuroscience
Psychomotor Performance
Zdroj: Journal of Alzheimer's disease : JAD. 17(3)
ISSN: 1875-8908
Popis: We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.
Databáze: OpenAIRE
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