Optogenetic neuromodulation with gamma oscillation as a new strategy for Alzheimer disease: a narrative review

Abstract

Alzheimer disease (AD), age-dependent dementia characterized by irreversible and progressive loss of memory and cognition, shows an approximately 11.3% prevalence in patients aged 65 years and older in the United States [1]. The prevalence of dementia was reported to be 10.2% in the Republic of Korea, of which approximately 74.5% were diagnosed with AD [2]. Both reports showed that the incidence of AD increases with age and that the prevalence of AD is expected to increase until 2050. The cause of AD is not completely understood [3], and its patho-The amyloid hypothesis has been considered a major explanation of the pathogenesis of Alzheimer disease. However, failure of phase III clinical trials with anti-amyloid-beta monoclonal antibodies reveals the need for other therapeutic approaches to treat Alzheimer disease. Compared to its relatively short history, optogenetics has developed considerably. The expression of microbial opsins in cells using genetic engineering allows specific control of cell signals or molecules. The application of optogenetics to Alzheimer disease research or clinical approaches is increasing. When applied with gamma entrainment, optogenetic neuromodulation can improve Alzheimer disease symptoms. Although safety problems exist with optogenetics such as the use of viral vectors, this technique has great potential for use in Alzheimer disease. In this paper, we review the historical applications of optogenetic neuromodulation with gamma entrainment to investigate the mechanisms involved in Alzheimer disease and potential therapeutic strategies.

Daily dynamics of resting-state EEG theta and gamma fluctuations are associated with cognitive performance in healthy aging

“…Studies in human aging have only found positive associations between local gamma power and β-amyloid burden in AD patients rather than gamma widespread synchrony (see Babiloni et al, 2021 for a review). Studies in human aging are increasingly carried out to clarify the association between gamma-band and βamyloid burden as gamma sensory stimulation is considered as a potential therapeutic strategy in AD (see Ko et al, 2022 for a review). We here provide arguments to consider gamma fluctuations as a marker of the progression of β-amyloid deposition.…”

Modulating Proteasome Function with Polyphenol Metabolites: A Promising Therapeutic Avenue for Alzheimer's Disease

“…The existing therapeutic landscape for AD emphasizes the pressing need for innovative approaches that target the root causes of the disease [5]. Aging-associated neurodegenerative diseases, characterized by progressive neuronal death and synapse loss in the human brain, are rapidly growing and affecting millions of people globally [6]. AD is clinically manifested by progressive impairment in cognition, learning ability, memory function, and executive reasoning [7].…”

Light-Controlled Modulation and Analysis of Neuronal Functions

“…By stimulating with light, this method provides high-spatiotemporal and high-specificity resolutions, in contrast to conventional pharmacological or electrical stimulation [ 18 , 19 ]. Optogenetics provides a route to study synaptic circuits [ 20 ] and underlying movement diseases [ 21 , 22 ] and has become an effective technology to revolutionize brain research for the therapy of vision [ 23 , 24 , 25 ], cardiovascular [ 26 ], and neurodegenerative disorders [ 27 , 28 ]. It has also been extended to other biomedical fields [ 29 , 30 ].…”