Gamma frequency entrainment attenuates amyloid load and modifies microglia

By Hunter F. Iaccarino, Annabelle C. Singer, Anthony J. Martorell, A. Rudenko, Fan Gao, Tyler Z Gillingham, H. Mathys, Jinsoo Seo, Oleg Kritskiy, Fatema Abdurrob and 6 more. Nature, 2016

1,002 citations recorded by the source corpus.

Changes in gamma oscillations (20–50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer’s disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1–40 and Aβ 1–42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ1–40 and Aβ1–42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer’s-disease-associated pathology.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/7c81e76a97f4410398d8aba821bfcedc7d467125

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Citations in the corpus

Multi-sensory gamma stimulation ameliorates Alzheimer’s-associated pathology and improves cognition. (2019, methodology): “Having shown that GENUS can be applied through both visual (Iaccarino et al., 2016) and auditory stimulation, we next aimed to investigate if a combination of 40 Hz auditory tone stimulation with 40 Hz light ﬂicker (combined GENUS) could entrain neural responses in AC, CA1, and mPFC and possibly…”
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “found that using noninvasive exposure to 40-Hz light for 1 h transformed microglia into an engulfing state, increased amyloid/microglia colocalization, and reduced Aβ load by 40–50% in an AD mouse model at early pre-plaque stage.(475) Similarly, Lechan Tao et al.”
Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution (2017, methodology): “Immunohistochemistry experiments were performed as described previously (Iaccarino et al., 2016).”
APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types (2018, positive): “Shorter process length of microglia in AD brains has been shown to positively correlate with microglial A b uptake (Iaccarino et al., 2016; Sarlus and He-neka, 2017).”
Temporal Interference Stimulation Enhances Neural Regeneration (2026, unknown): “A significant increase in cell density was found in the low gamma condition, which is in line with previous literature [ 81 ].”
Auditory gamma-band entrainment enhances default mode network connectivity in dementia patients (2024, methodology): “Exposure to flickering light at 40 Hz has been shown to produce a similar effect in the visual cortex 20,34,35 .”
Neural Mechanisms Underlying Brain Gamma Entrainment after Periodic Auditory Stimulation at Gamma Frequency (2024, background): “However, other evidence shows that network disruption, such as reduced brain oscillation, occurred before the loss of synapses [16–18].”