[
Adamantane
/ analogs & derivatives
Alzheimer Disease
/ diagnostic imaging
Amyloid beta-Peptides
/ metabolism
Animals
Brain
/ metabolism
Cognitive Dysfunction
/ diagnostic imaging
Histone Deacetylase 1
/ metabolism
Histone Deacetylases
/ genetics
Humans
Hydroxamic Acids
Positron-Emission Tomography
/ methods
Rats
tau Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 07 2022
19 07 2022
Historique:
received:
21
07
2020
accepted:
04
05
2022
entrez:
19
7
2022
pubmed:
20
7
2022
medline:
22
7
2022
Statut:
epublish
Résumé
Alzheimer's disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-β, tau, and class I histone deacetylase (HDAC I isoforms 1-3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-β PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-β and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-β plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.
Identifiants
pubmed: 35853847
doi: 10.1038/s41467-022-30653-5
pii: 10.1038/s41467-022-30653-5
pmc: PMC9296476
doi:
Substances chimiques
Amyloid beta-Peptides
0
Hydroxamic Acids
0
tau Proteins
0
martinostat
8JJC99KHGL
HDAC1 protein, human
EC 3.5.1.98
Hdac1 protein, rat
EC 3.5.1.98
Histone Deacetylase 1
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Adamantane
PJY633525U
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4171Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014296
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA030321
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR017208
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026666
Pays : United States
Organisme : CIHR
ID : FRN 152985
Pays : Canada
Organisme : NIA NIH HHS
ID : R01 AG073267
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG051987
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR022976
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG075336
Pays : United States
Organisme : CIHR
ID : MOP-11-51-31
Pays : Canada
Organisme : NCRR NIH HHS
ID : S10 RR019933
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015896
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG051931
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023401
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
Jack, C. R. Jr. et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12, 207–216 (2013).
pubmed: 23332364
pmcid: 3622225
doi: 10.1016/S1474-4422(12)70291-0
Graff, J. et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483, 222–226 (2012).
pubmed: 22388814
pmcid: 3498952
doi: 10.1038/nature10849
Graff, J. & Tsai, L. H. Histone acetylation: molecular mnemonics on the chromatin. Nat. Rev. Neurosci. 14, 97–111 (2013).
pubmed: 23324667
doi: 10.1038/nrn3427
Dulac, C. Brain function and chromatin plasticity. Nature 465, 728–735 (2010).
pubmed: 20535202
pmcid: 3075582
doi: 10.1038/nature09231
Guan, J. S. et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459, 55–60 (2009).
pubmed: 19424149
pmcid: 3498958
doi: 10.1038/nature07925
Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M. & Tsai, L. H. Recovery of learning and memory is associated with chromatin remodelling. Nature 447, 178–182 (2007).
pubmed: 17468743
doi: 10.1038/nature05772
Falkenberg, K. J. & Johnstone, R. W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov. 13, 673–691 (2014).
pubmed: 25131830
doi: 10.1038/nrd4360
Peleg, S. et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328, 753–756 (2010).
pubmed: 20448184
doi: 10.1126/science.1186088
Lattal, K. M. & Wood, M. A. Epigenetics and persistent memory: implications for reconsolidation and silent extinction beyond the zero. Nat. Neurosci. 16, 124–129 (2013).
pubmed: 23354385
pmcid: 3740093
doi: 10.1038/nn.3302
Sweatt, J. D. Behavioural neuroscience: down memory lane. Nature 447, 151–152 (2007).
pubmed: 17468746
doi: 10.1038/nature05716
Jakovcevski, M. & Akbarian, S. Epigenetic mechanisms in neurological disease. Nat. Med. 18, 1194–1204 (2012).
pubmed: 22869198
pmcid: 3596876
doi: 10.1038/nm.2828
Zhu, X. et al. HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer’s disease. Aging Cell 16, 1073–1082 (2017).
pubmed: 28771976
pmcid: 5595690
doi: 10.1111/acel.12642
Mahady, L. et al. Frontal cortex epigenetic dysregulation during the progression of Alzheimer’s Disease. J. Alzheimer’s Dis. 62, 115–131 (2018).
doi: 10.3233/JAD-171032
Yamakawa, H. et al. The transcription factor Sp3 cooperates with HDAC2 to regulate synaptic function and plasticity in neurons. Cell Rep. 20, 1319–1334 (2017).
pubmed: 28793257
doi: 10.1016/j.celrep.2017.07.044
Gonzalez-Zuniga, M. et al. c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer’s disease. Mol. Cell 56, 163–173 (2014).
pubmed: 25219501
doi: 10.1016/j.molcel.2014.08.013
Bie, B. et al. Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency. Nat. Neurosci. 17, 223–231 (2014).
pubmed: 24441681
doi: 10.1038/nn.3618
Yang, S. S., Zhang, R., Wang, G. & Zhang, Y. F. The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease. Transl. Neurodegener. 6, 19 (2017).
pubmed: 28702178
pmcid: 5504819
doi: 10.1186/s40035-017-0089-1
Xu, K., Dai, X. L., Huang, H. C. & Jiang, Z. F. Targeting HDACs: a promising therapy for Alzheimer’s disease. Oxid. Med. Cell. Longev. 2011, 143269 (2011).
pubmed: 21941604
pmcid: 3177096
doi: 10.1155/2011/143269
Kilgore, M. et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 35, 870–880 (2010).
pubmed: 20010553
doi: 10.1038/npp.2009.197
Cuadrado-Tejedor, M. et al. A First-in-Class small-molecule that acts as a dual inhibitor of HDAC and PDE5 and that rescues hippocampal synaptic impairment in Alzheimer’s disease mice. Neuropsychopharmacology 42, 524–539 (2017).
pubmed: 27550730
doi: 10.1038/npp.2016.163
Cummings, J., Lee, G., Ritter, A. & Zhong, K. Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement. (N. Y) 4, 195–214 (2018).
doi: 10.1016/j.trci.2018.03.009
Anderson, K. W. et al. Quantification of histone deacetylase isoforms in human frontal cortex, human retina, and mouse brain. PLoS ONE 10, e0126592 (2015).
pubmed: 25962138
pmcid: 4427357
doi: 10.1371/journal.pone.0126592
Schueller, E. et al. Dysregulation of histone acetylation pathways in hippocampus and frontal cortex of Alzheimer’s disease patients. Eur. Neuropsychopharmacol. https://doi.org/10.1016/j.euroneuro.2020.01.015 (2020).
Wey, H. Y. et al. Insights into neuroepigenetics through human histone deacetylase PET imaging. Sci. Transl. Med. 8, 351ra106 (2016).
pubmed: 27510902
pmcid: 5784409
doi: 10.1126/scitranslmed.aaf7551
Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 (1991).
pubmed: 1759558
doi: 10.1007/BF00308809
Pascoal, T. A. et al. Amyloid-beta and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer’s disease. Mol. Psychiatry 22, 306–311 (2017).
pubmed: 27021814
doi: 10.1038/mp.2016.37
Kim, D. et al. Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron 60, 803–817 (2008).
pubmed: 19081376
pmcid: 2912147
doi: 10.1016/j.neuron.2008.10.015
Akhtar, M. W. et al. Histone deacetylases 1 and 2 form a developmental switch that controls excitatory synapse maturation and function. J. Neurosci. 29, 8288–8297 (2009).
pubmed: 19553468
pmcid: 2895817
doi: 10.1523/JNEUROSCI.0097-09.2009
Montgomery, R. L., Hsieh, J., Barbosa, A. C., Richardson, J. A. & Olson, E. N. Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc. Natl Acad. Sci. USA 106, 7876–7881 (2009).
pubmed: 19380719
pmcid: 2683090
doi: 10.1073/pnas.0902750106
Jiang, Y. & Hsieh, J. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels. Proc. Natl Acad. Sci. USA 111, 13541–13546 (2014).
pubmed: 25161285
pmcid: 4169927
doi: 10.1073/pnas.1411939111
Jeong, H. et al. Pan-HDAC inhibitors promote tau aggregation by increasing the level of acetylated Tau. Int. J. Mol. Sci. 20, https://doi.org/10.3390/ijms20174283 (2019).
Pao, P. C. et al. HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease. Nat. Commun. 11, 2484 (2020).
pubmed: 32424276
pmcid: 7235043
doi: 10.1038/s41467-020-16361-y
Fleisher, A. S. et al. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology 77, 1263–1271 (2011).
pubmed: 21917762
pmcid: 3179645
doi: 10.1212/WNL.0b013e318230a16c
Beach, T. G., Monsell, S. E., Phillips, L. E. & Kukull, W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010. J. Neuropathol. Exp. Neurol. 71, 266–273 (2012).
pubmed: 22437338
doi: 10.1097/NEN.0b013e31824b211b
Mirra, S. S. et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41, 479–486 (1991).
pubmed: 2011243
doi: 10.1212/WNL.41.4.479
Do Carmo, S. & Cuello, A. C. Modeling Alzheimer’s disease in transgenic rats. Mol. Neurodegener. 8, 37 (2013).
pubmed: 24161192
pmcid: 4231465
doi: 10.1186/1750-1326-8-37
Cohen, R. M. et al. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric abeta, and frank neuronal loss. J. Neurosci. 33, 6245–6256 (2013).
pubmed: 23575824
pmcid: 3720142
doi: 10.1523/JNEUROSCI.3672-12.2013
Pascoal, T. A. et al. In vivo quantification of neurofibrillary tangles with [(18)F]MK-6240. Alzheimers Res. Ther. 10, 74 (2018).
pubmed: 30064520
pmcid: 6069775
doi: 10.1186/s13195-018-0402-y
Cselenyi, Z. et al. Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. J. Nucl. Med. 53, 415–424 (2012).
pubmed: 22323782
doi: 10.2967/jnumed.111.094029
Thomas, B. A. et al. The importance of appropriate partial volume correction for PET quantification in Alzheimer’s disease. Eur. J. Nucl. Med. Mol. Imaging 38, 1104–1119 (2011).
pubmed: 21336694
doi: 10.1007/s00259-011-1745-9
Klein, A. & Tourville, J. 101 labeled brain images and a consistent human cortical labeling protocol. Front. Neurosci. 6, 171 (2012).
pubmed: 23227001
pmcid: 3514540
doi: 10.3389/fnins.2012.00171
Lammertsma, A. A. & Hume, S. P. Simplified reference tissue model for PET receptor studies. NeuroImage 4, 153–158 (1996).
pubmed: 9345505
doi: 10.1006/nimg.1996.0066
Joseph-Mathurin, N. et al. Utility of perfusion PET measures to assess neuronal injury in Alzheimer’s disease. Alzheimers Dement. (Amstradam) 10, 669–677 (2018).
doi: 10.1016/j.dadm.2018.08.012
Chen, Y. J. et al. Relative 11C-PiB delivery as a proxy of relative CBF: quantitative evaluation using single-session 15O-water and 11C-PiB PET. J. Nucl. Med. 56, 1199–1205 (2015).
pubmed: 26045309
doi: 10.2967/jnumed.114.152405
Rodriguez-Vieitez, E. et al. Comparability of [(18)F]THK5317 and [(11)C]PIB blood flow proxy images with [(18)F]FDG positron emission tomography in Alzheimer’s disease. J. Cereb. Blood Flow Metab. 37, 740–749 (2017).
pubmed: 27107028
doi: 10.1177/0271678X16645593
Hsiao, I. T. et al. Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur. J. Nucl. Med. Mol. Imaging 39, 613–620 (2012).
pubmed: 22270508
doi: 10.1007/s00259-011-2051-2
Wey, H. Y. et al. Kinetic analysis and quantification of [(1)(1)C]Martinostat for in vivo HDAC imaging of the brain. ACS Chem. Neurosci. 6, 708–715 (2015).
pubmed: 25768025
doi: 10.1021/acschemneuro.5b00066
Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012).
pubmed: 22996553
pmcid: 4243026
doi: 10.1038/nature11405
Gryglewski, G. et al. Spatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging. NeuroImage 176, 259–267 (2018).
pubmed: 29723639
doi: 10.1016/j.neuroimage.2018.04.068
Smith, R., Wibom, M., Pawlik, D., Englund, E. & Hansson, O. Correlation of in vivo [18F]Flortaucipir with postmortem Alzheimer disease tau pathology. JAMA Neurol. 76, 310–317 (2019).
pubmed: 30508025
doi: 10.1001/jamaneurol.2018.3692
Montine, T. J. et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol. 123, 1–11 (2012).
pubmed: 22101365
doi: 10.1007/s00401-011-0910-3
Mathotaarachchi, S. et al. VoxelStats: a MATLAB package for multi-modal voxel-wise brain image analysis. Front. Neuroinform. 10, 20 (2016).
pubmed: 27378902
pmcid: 4908129
doi: 10.3389/fninf.2016.00020
Kievit, R. A. et al. Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking. Nat. Commun. 5, 5658 (2014).
pubmed: 25519467
doi: 10.1038/ncomms6658
Pascoal, T. A. et al. [11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease. https://doi.org/10.5281/zenodo.6388101 (2022).