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

Abstract

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.

Finding Drug Repurposing Candidates for Neurodegenerative Diseases using Zebrafish Behavioral Profiles

“…β-adrenergic receptors (βARs) are G protein-coupled receptors (GPCRs) responsible for regulating synaptic plasticity and memory formation (Kemp & Manahan-Vaughan, 2008). Specifically, β2-adrenergic receptor (β2AR) agonists are emerging therapeutic targets for neurological diseases (Li, 2023). During our screening, we found 5 β2AR agonists of interest with varying levels of supporting literature in the context of AD.…”

Periodontal disease and risk of Alzheimer's disease: A two‐sample Mendelian randomization

“…Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by the progressive accumulation of beta‐amyloid (Aβ) plaques and tau neurofibrillary tangles within the brain parenchyma, which are closely associated with widespread cerebral inflammatory processes (Li, 2023 ; Small et al., 1997 ). These pathological markers contribute to the gradual deterioration of cognitive function and the development of progressive memory impairments.…”

Confounding in observational studies evaluating the association between Alzheimer's disease and periodontal disease: A systematic review

“…Over the years, periodontitis has been associated with several systemic conditions, including diabetes, cardiovascular diseases, and mortality. More recently, studies have investigated the association between periodontitis and Alzheimer's disease (AD), a complex neurodegenerative disorder defined by a progressive accumulation of cerebral parenchymal β-Amyloid (Aβ) plaques and intraneuronal tau neurofibrillary tangles, associated with extensive brain inflammatory processes, leading to a gradual cognitive decline with progressive memory impairment [ 8 , 9 ]. It is estimated that there will be approximately 152 million people with AD and other forms of dementia by 2050 [ 10 ].…”