The β-adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein-induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at the prodromal stage of AD, activation of adrenergic receptors could serve as the first line of defense against the onset of the disease. Activation of β₂ -ARs strengthens long-term potentiation (LTP) and synaptic activity, thus improving learning and memory. Physical stimulation of animals exposed to an enriched environment (EE) leads to the activation of β₂ -ARs and prevents synaptic dysfunction. EE also suppresses neuroinflammation, suggesting that β₂ -AR agonists may play a neuroprotective role. The β₂ -AR agonists used for respiratory diseases have been shown to have an anti-inflammatory effect. Epidemiological studies further support the beneficial effects of β₂ -AR agonists on several neurodegenerative diseases. Thus, I propose that β₂ -AR agonists may provide therapeutic value in combination with novel treatments for AD.