Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease

Caterina Branca, Elena V. Wisely, Lauren K. Hartman, Antonella Caccamo, Salvatore Oddo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Currently, there are no available approaches to cure or slow down the progression of Alzheimer's disease (AD), which is characterized by the accumulation of extracellular amyloid-β (Aβ) deposits and intraneuronal tangles that comprised hyperphosphorylated tau. The β2 adrenergic receptors (β2ARs) are expressed throughout the cortex and hippocampus and play a key role in cognitive functions. Alterations in the function of these receptors have been linked to AD; however, these data remain controversial as apparent contradicting reports have been published. Given the current demographics of growing elderly population and the high likelihood of concurrent β-blocker use for other chronic conditions, more studies into the role of this receptor in AD animal models are needed. Here, we show that administration of ICI 118,551 (ICI), a selective β2AR antagonist, exacerbates cognitive deficits in a mouse model of AD, the 3xTg-AD mice. Neuropathologically, ICI increased Aβ levels and Aβ plaque burden. Concomitantly, ICI-treated 3xTg-AD mice showed an increase in tau phosphorylation and accumulation. Mechanistically, these changes were linked to an increase in amyloidogenic amyloid precursor protein processing. These results suggest that under the conditions used here, selective pharmacologic inhibition of β2ARs has detrimental effects on AD-like pathology in mice. Overall, these studies strengthen the notion that the link between β2ARs and AD is likely highly complex and suggest caution in generalizing the beneficial effects of β blockers on AD.

Original languageEnglish (US)
Pages (from-to)2726-2735
Number of pages10
JournalNeurobiology of Aging
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Adrenergic Antagonists
Alzheimer Disease
Adrenergic Receptors
Amyloidogenic Proteins
Neuropathology
Amyloid Plaques
Amyloid
Cognition
Hippocampus
Animal Models
Phosphorylation
Demography
Pathology

Keywords

  • APP
  • Tangles
  • Tau
  • β Blockers

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease. / Branca, Caterina; Wisely, Elena V.; Hartman, Lauren K.; Caccamo, Antonella; Oddo, Salvatore.

In: Neurobiology of Aging, Vol. 35, No. 12, 01.12.2014, p. 2726-2735.

Research output: Contribution to journalArticle

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