Caffeine suppresses amyloid-β levels in plasma and brain of alzheimer's disease transgenic mice

Chuanhai Cao, John R. Cirrito, Xiaoyang Lin, Lilly Wang, Deborah K. Verges, Alexander Dickson, Malgorzata Mamcarz, Chi Zhang, Takashi Mori, Gary W. Arendash, David M. Holtzman, Huntington Potter

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-β (Aβ) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Aβ levels in both brain interstitial fluid and plasma without affecting Aβ elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Aβ, but also decreases in both soluble and deposited Aβ in hippocampus and cortex. Irrespective of caffeine treatment, plasma Aβ levels did not correlate with brain Aβ levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Aβ-{1-40} levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Aβ levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Aβ levels are not an accurate index of brain Aβ levels/deposition or cognitive performance in aged AD mice.

Original languageEnglish
Pages (from-to)681-697
Number of pages17
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2009


  • Alzheimer's disease
  • Amyloid-β
  • Brain interstitial fluid
  • Caffeine
  • Plasma
  • Transgenic mice


Dive into the research topics of 'Caffeine suppresses amyloid-β levels in plasma and brain of alzheimer's disease transgenic mice'. Together they form a unique fingerprint.

Cite this