Propranolol reduces cognitive deficits, amyloid and tau pathology in Alzheimer's transgenic mice

Abstract

The efficacy of antihypertensive agents in Alzheimer's disease (AD) is controversial. It has been tested here whether some antihypertensive drugs might influence AD through mechanisms independent of blood pressure-lowering activity. The effects of treatment with the antihypertensive propranolol on cognition and AD-related markers have been studied in the Tg2576 mouse model of AD. Propranolol, at a lower dose than that used as antihypertensive (5 mg/kg, 6 wk), attenuated cognitive impairments shown by Tg2576 mice aged 9 months in the novel object recognition and fear conditioning tests. Propranolol was also able to counteract the increases in hippocampal levels of Aβ(42) present in Tg2576 mice. This effect was accompanied by an increased expression of insulin degrading enzyme. Changes in markers of synaptic pathology, as shown by decreases in phosphorylation of Akt and in the expression of BDNF in Tg2676 mice, were also counteracted by propranolol treatment. Tau hyperphosphorylation shown by Tg2576 mice was also decreased in the hippocampus of propranolol-treated mice, an effect probably related to an increase of GSK3β phosphorylation (inactive form) and a decreased JNK1 expression. Overall, these data further strengthen the potential of propranolol as a therapeutic agent for AD.

Behavioral assays with mouse models of Alzheimer's disease: Practical considerations and guidelines

“…Consistent with these findings, the Tg2576 mouse model showed an impairment of contextual fear learning at 4–6 months [78–82] when plaques are not yet detectable, but the Aβ42:Aβ40 ratio is modified [80]. This defect worsens with age, [78, 182] and becomes profound at 12–14 months [183, 184]. It should be also noted that the same animals have provided different results in different studies assessing cued learning which was found to be either normal [183, 184] or altered [185].…”

Central and Peripheral Administration of Antisense Oligonucleotide Targeting Amyloid-β Protein Precursor Improves Learning and Memory and Reduces Neuroinflammatory Cytokines in Tg2576 (AβPPswe) Mice

“…Tg2576 mice have been reported to have deficits in object recognition [24, 25]. We have shown that OL-1 reverses deficits in object recognition in SAMP8 mice [15].…”

“…Tg2576 mice have been reported to have behavioral disinhibition that increases with age compared to the wild type controls [24, 28]. At 9 months of age Tg2576 mice spent significantly greater amount of time in the open arms of an elevated plus maze compared to wild type controls [28] and would freeze less when presented with a loud tone compared to wild type controls [28].…”

One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition

“…Propranolol, the β-blocker found to ameliorate the stress-induced upregulation of pro-inflammatory myelopoiesis [99], attenuated cognitive deficits, amyloid accumulation, and tau phosphorylation in AD transgenic mice [27]. Genetic inhibition of β2-adrenergic receptors in particular has been shown to reduce tau pathology [138].…”