Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer's Disease: A Case Series.
Amyloid
dementia
electroencephalography
gamma
neurostimulation
positron-emission tomography
protein clearance
protein misfolding
tau
transcranial electrical stimulation
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2022
2022
Historique:
pubmed:
28
12
2021
medline:
4
3
2022
entrez:
27
12
2021
Statut:
ppublish
Résumé
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. We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34958021
pii: JAD215072
doi: 10.3233/JAD-215072
pmc: PMC9023125
mid: NIHMS1789598
doi:
Substances chimiques
Amyloid beta-Peptides
0
tau Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1667-1676Subventions
Organisme : NIA NIH HHS
ID : P01 AG031720
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB022544
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060981
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117063
Pays : United States
Références
Neurology. 2000;54(11 Suppl 5):S10-5
pubmed: 10854355
Cortex. 2016 Feb;75:33-43
pubmed: 26707084
Science. 2020 Oct 2;370(6512):66-69
pubmed: 33004513
Science. 2020 Oct 2;370(6512):50-56
pubmed: 33004510
Nat Neurosci. 2020 Oct;23(10):1183-1193
pubmed: 32778792
Neuroimage Clin. 2017 May 13;15:325-332
pubmed: 28560157
Sci Transl Med. 2021 Jan 20;13(577):
pubmed: 33472953
J Nucl Med. 2005 Dec;46(12):1959-72
pubmed: 16330558
PLoS One. 2017 Jan 23;12(1):e0170275
pubmed: 28114405
Cell. 2019 Apr 4;177(2):256-271.e22
pubmed: 30879788
Science. 2005 May 27;308(5726):1314-8
pubmed: 15831717
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
JAMA Neurol. 2019 Aug 01;76(8):915-924
pubmed: 31157827
Data Brief. 2017 Oct 16;15:648-657
pubmed: 29124088
J Inherit Metab Dis. 2018 Jul 13;:
pubmed: 30006770
Nature. 2016 Dec 7;540(7632):230-235
pubmed: 27929004
J Nucl Med. 2009 Mar;50(3):348-55
pubmed: 19223409
J Neurosci. 2015 Nov 25;35(47):15716-30
pubmed: 26609163
EJNMMI Res. 2020 Oct 19;10(1):123
pubmed: 33074395
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
Ageing Res Rev. 2016 Aug;29:66-89
pubmed: 27221544
Int J Psychophysiol. 2016 May;103:88-102
pubmed: 25660305
Brain. 2019 Oct 1;142(10):3230-3242
pubmed: 31501889
Brain. 2017 Dec 1;140(12):3286-3300
pubmed: 29053874
Brain. 2013 Jul;136(Pt 7):2228-38
pubmed: 23775979
Lancet Neurol. 2013 Apr;12(4):357-67
pubmed: 23477989
Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9
pubmed: 9236950
J Nucl Med. 2018 Jun;59(6):937-943
pubmed: 29284675
EJNMMI Res. 2016 Dec;6(1):72
pubmed: 27678494
JAMA Psychiatry. 2020 Jan 1;77(1):7-8
pubmed: 31532462
Nat Neurosci. 2010 Jul;13(7):812-8
pubmed: 20581818
Neuroimage. 2006 Jul 1;31(3):968-80
pubmed: 16530430
Front Neurosci. 2020 Jun 30;14:705
pubmed: 32714142
Neuron. 2019 Jun 5;102(5):929-943.e8
pubmed: 31076275
Nat Rev Neurosci. 2016 Dec;17(12):777-792
pubmed: 27829687
Am J Psychiatry. 1984 Nov;141(11):1356-64
pubmed: 6496779
J Am Geriatr Soc. 2005 Apr;53(4):695-9
pubmed: 15817019
Neurology. 2013 Mar 5;80(10):890-6
pubmed: 23446680
Alzheimers Dement. 2020 Nov;16(11):1483-1492
pubmed: 33049114
Brain. 2017 Mar 1;140(3):748-763
pubmed: 28077397
Curr Biol. 2013 Aug 5;23(15):1449-53
pubmed: 23891115
J Nucl Med. 2015 May;56(5):701-6
pubmed: 25766898
Brain Res Bull. 2017 May;131:47-54
pubmed: 28322886
Ann Neurol. 2016 Jan;79(1):110-9
pubmed: 26505746
Nature. 2018 Mar 1;555(7694):20-22
pubmed: 29493598
Nat Rev Neurol. 2021 Mar;17(3):157-172
pubmed: 33318676
Neuron. 2010 Jul 15;67(1):129-43
pubmed: 20624597
Sci Rep. 2019 Apr 8;9(1):5778
pubmed: 30962465
Ann Neurol. 2004 Mar;55(3):306-19
pubmed: 14991808