Maeva Dhaynaut1, Giulia Sprugnoli2, Davide Cappon2, Joanna Macone2, Justin S Sanchez1,3, Marc D Normandin1, Nicolas J Guehl1, Giacomo Koch4,5, Rachel Paciorek2, Ann Connor2, Daniel Press2, Keith Johnson1,3, Alvaro Pascual-Leone6,7, Georges El Fakhri1, Emiliano Santarnecchi1,2. 1. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 4. Santa Lucia Foundation IRCCS, Rome, Italy. 5. Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy. 6. Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA. 7. Department of Neurology, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Alzheimer's disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models. OBJECTIVE: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). METHODS: Four participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. RESULTS: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. CONCLUSION: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.
BACKGROUND: Alzheimer's disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models. OBJECTIVE: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). METHODS: Four participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. RESULTS: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. CONCLUSION: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.
Entities:
Keywords:
Amyloid; dementia; electroencephalography; gamma; neurostimulation; positron-emission tomography; protein clearance; protein misfolding; tau; transcranial electrical stimulationzzm321990
Authors: Brian J Lopresti; William E Klunk; Chester A Mathis; Jessica A Hoge; Scott K Ziolko; Xueling Lu; Carolyn C Meltzer; Kurt Schimmel; Nicholas D Tsopelas; Steven T DeKosky; Julie C Price Journal: J Nucl Med Date: 2005-12 Impact factor: 10.057
Authors: L Fratiglioni; L J Launer; K Andersen; M M Breteler; J R Copeland; J F Dartigues; A Lobo; J Martinez-Lage; H Soininen; A Hofman Journal: Neurology Date: 2000 Impact factor: 9.910
Authors: Ksenia V Kastanenka; Steven S Hou; Naomi Shakerdge; Robert Logan; Danielle Feng; Susanne Wegmann; Vanita Chopra; Jonathan M Hawkes; Xiqun Chen; Brian J Bacskai Journal: PLoS One Date: 2017-01-23 Impact factor: 3.240
Authors: Justin S Sanchez; J Alex Becker; Heidi I L Jacobs; Bernard J Hanseeuw; Shu Jiang; Aaron P Schultz; Michael J Properzi; Samantha R Katz; Alexa Beiser; Claudia L Satizabal; Adrienne O'Donnell; Charles DeCarli; Ron Killiany; Georges El Fakhri; Marc D Normandin; Teresa Gómez-Isla; Yakeel T Quiroz; Dorene M Rentz; Reisa A Sperling; Sudha Seshadri; Jean Augustinack; Julie C Price; Keith A Johnson Journal: Sci Transl Med Date: 2021-01-20 Impact factor: 17.956
Authors: Santiago Bullich; John Seibyl; Ana M Catafau; Aleksandar Jovalekic; Norman Koglin; Henryk Barthel; Osama Sabri; Susan De Santi Journal: Neuroimage Clin Date: 2017-05-13 Impact factor: 4.881
Authors: Julius Kricheldorff; Katharina Göke; Maximilian Kiebs; Florian H Kasten; Christoph S Herrmann; Karsten Witt; Rene Hurlemann Journal: Brain Sci Date: 2022-07-15
Authors: Yang Liu; Can Tang; Kailun Wei; Di Liu; Keke Tang; Meilian Chen; Xuewei Xia; Zhiqi Mao Journal: Front Neurol Date: 2022-09-23 Impact factor: 4.086