| First Author | Branca C | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 12 | Pages | 2726-2735 |
| PubMed ID | 25034342 | Mgi Jnum | J:218068 |
| Mgi Id | MGI:5616506 | Doi | 10.1016/j.neurobiolaging.2014.06.011 |
| Citation | Branca C, et al. (2014) Administration of a selective beta2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease. Neurobiol Aging 35(12):2726-2735 |
| abstractText | 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-beta (Abeta) deposits and intraneuronal tangles that comprised hyperphosphorylated tau. The beta2 adrenergic receptors (beta2ARs) 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 beta-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 beta2AR antagonist, exacerbates cognitive deficits in a mouse model of AD, the 3xTg-AD mice. Neuropathologically, ICI increased Abeta levels and Abeta 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 beta2ARs has detrimental effects on AD-like pathology in mice. Overall, these studies strengthen the notion that the link between beta2ARs and AD is likely highly complex and suggest caution in generalizing the beneficial effects of beta blockers on AD. |
