Association between lower body temperature and increased tau pathology in cognitively normal older adults.
Aging
Alzheimer's disease
Body temperature
Neurofibrillary tangle
Phosphorylation
Tau
[(18)F]MK-6240
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
04
01
2022
revised:
25
04
2022
accepted:
05
05
2022
pubmed:
14
5
2022
medline:
27
7
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
Preclinical studies suggest body temperature (Tb) and consequently brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD). Tau phosphorylation is substantially increased by a small (<1 °C) decrease in temperature within the human physiological range, and thermoregulatory nuclei are affected by tau pathology early in the AD continuum. In this study we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults. Tb was continuously measured with ingestible telemetry sensors for 48 h. This period included two nights of nocturnal polysomnography to delineate whether Tb during waking vs sleep is differentially associated with tau pathology. Tau phosphorylation was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement. In addition, neurofibrillary tangle (NFT) burden in early Braak stage regions was imaged with PET-MR using the [18F]MK-6240 radiotracer on average one month later. Lower Tb was associated with increased NFT burden, as well as increased plasma and CSF P-tau levels (p < 0.05). NFT burden was associated with lower Tb during waking (p < 0.05) but not during sleep intervals. Plasma and CSF P-tau levels were highly correlated with each other (p < 0.05), and both variables were correlated with tau tangle radiotracer uptake (p < 0.05). These results, the first available for human, suggest that lower Tb in older adults may be associated with increased tau pathology. Our findings add to the substantial preclinical literature associating lower body and brain temperature with tau hyperphosphorylation. NCT03053908.
Sections du résumé
BACKGROUND
Preclinical studies suggest body temperature (Tb) and consequently brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD). Tau phosphorylation is substantially increased by a small (<1 °C) decrease in temperature within the human physiological range, and thermoregulatory nuclei are affected by tau pathology early in the AD continuum. In this study we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults.
METHODS
Tb was continuously measured with ingestible telemetry sensors for 48 h. This period included two nights of nocturnal polysomnography to delineate whether Tb during waking vs sleep is differentially associated with tau pathology. Tau phosphorylation was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement. In addition, neurofibrillary tangle (NFT) burden in early Braak stage regions was imaged with PET-MR using the [18F]MK-6240 radiotracer on average one month later.
RESULTS
Lower Tb was associated with increased NFT burden, as well as increased plasma and CSF P-tau levels (p < 0.05). NFT burden was associated with lower Tb during waking (p < 0.05) but not during sleep intervals. Plasma and CSF P-tau levels were highly correlated with each other (p < 0.05), and both variables were correlated with tau tangle radiotracer uptake (p < 0.05).
CONCLUSIONS
These results, the first available for human, suggest that lower Tb in older adults may be associated with increased tau pathology. Our findings add to the substantial preclinical literature associating lower body and brain temperature with tau hyperphosphorylation.
CLINICAL TRIAL NUMBER
NCT03053908.
Identifiants
pubmed: 35550158
pii: S0969-9961(22)00140-1
doi: 10.1016/j.nbd.2022.105748
pmc: PMC9751849
mid: NIHMS1856912
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
tau Proteins
0
Banques de données
ClinicalTrials.gov
['NCT03053908']
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
105748Subventions
Organisme : NHLBI NIH HHS
ID : K25 HL151912
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG013616
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066870
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG012101
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066514
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057570
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG022374
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058913
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG055002
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Références
Mol Metab. 2019 Apr;22:110-120
pubmed: 30770297
Neurobiol Aging. 1982 Winter;3(4):299-309
pubmed: 7170047
Alzheimers Res Ther. 2021 Mar 25;13(1):65
pubmed: 33766131
Brain. 2019 Jan 1;143(1):320-335
pubmed: 31886494
Gerontology. 1986;32(2):110-8
pubmed: 3710170
J Biol Chem. 1984 Apr 25;259(8):5301-5
pubmed: 6425287
J Nucl Med. 2022 Jan;63(1):108-116
pubmed: 33863821
Acta Neuropathol. 2017 May;133(5):665-704
pubmed: 28386764
Alzheimers Dement. 2018 Nov;14(11):1470-1481
pubmed: 29499171
Lancet Neurol. 2006 Mar;5(3):228-34
pubmed: 16488378
Science. 2010 Oct 15;330(6002):379-85
pubmed: 20947768
Am J Physiol Regul Integr Comp Physiol. 2013 Sep;305(5):R478-89
pubmed: 23824962
Brain. 2020 Sep 1;143(9):2818-2830
pubmed: 32671408
J Gerontol. 1984 Jan;39(1):30-5
pubmed: 6690585
Front Neuroanat. 2021 Feb 02;15:592288
pubmed: 33603651
Sleep. 1991 Dec;14(6):478-85
pubmed: 1798879
Prev Med Rep. 2020 Oct 02;20:101221
pubmed: 33088678
Philos Trans R Soc Lond B Biol Sci. 2013 Dec 02;369(1633):20130144
pubmed: 24298146
Altern Med Rev. 2006 Dec;11(4):278-93
pubmed: 17176167
Sci Rep. 2018 Feb 16;8(1):3184
pubmed: 29453339
Brain Pathol. 2016 May;26(3):371-86
pubmed: 26193084
J Clin Invest. 2007 Mar;117(3):648-58
pubmed: 17304350
J Neurosci. 2011 Nov 2;31(44):15944-55
pubmed: 22049437
J Exp Biol. 2015 Jun;218(Pt 12):1801-11
pubmed: 26085658
J Alzheimers Dis. 2015;49(1):93-100
pubmed: 26444757
Neurobiol Aging. 1997 Jan-Feb;18(1):105-9
pubmed: 8983038
Brain. 2008 Jun;131(Pt 6):1609-17
pubmed: 18372313
Neurobiol Aging. 2016 Jul;43:47-57
pubmed: 27255814
J Biol Rhythms. 2002 Feb;17(1):4-13
pubmed: 11837947
Front Biosci (Landmark Ed). 2010 Jan 01;15(2):564-94
pubmed: 20036834
J Korean Med Sci. 2020 Nov 16;35(44):e361
pubmed: 33200589
Mol Cell. 2017 Aug 3;67(3):433-446.e4
pubmed: 28689656
Brain. 2020 Aug 1;143(8):2576-2593
pubmed: 32705145
Curr Alzheimer Res. 2016;13(10):1178-97
pubmed: 27264543
Neuropathol Appl Neurobiol. 2009 Aug;35(4):406-16
pubmed: 19508444
Neurobiol Aging. 1995 Sep-Oct;16(5):765-71
pubmed: 8532109
Alzheimers Dement. 2019 Oct;15(10):1253-1263
pubmed: 31416793
Front Endocrinol (Lausanne). 2017 Jun 13;8:130
pubmed: 28659868
Lancet. 2021 Apr 24;397(10284):1577-1590
pubmed: 33667416
J Neural Transm (Vienna). 2015 Apr;122(4):531-9
pubmed: 25480630
J Gerontol A Biol Sci Med Sci. 2011 May;66(5):487-92
pubmed: 21324956
J Biol Chem. 2001 Sep 7;276(36):34298-306
pubmed: 11441005
J Neurosci. 2003 Aug 6;23(18):6972-81
pubmed: 12904458
Science. 2019 Feb 22;363(6429):880-884
pubmed: 30679382
Neurobiol Aging. 2004 Jul;25(6):771-81
pubmed: 15165702
FASEB J. 2009 Aug;23(8):2595-604
pubmed: 19279139
Science. 2019 Nov 1;366(6465):628-631
pubmed: 31672896
Biol Psychiatry. 1989 Nov;26(7):736-40
pubmed: 2804195
Lancet Neurol. 2018 Nov;17(11):1016-1024
pubmed: 30353860
PLoS One. 2011 Jan 18;6(1):e14530
pubmed: 21267079
Am J Geriatr Psychiatry. 2005 May;13(5):359-68
pubmed: 15879584
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):87-92
pubmed: 17190808
Sleep. 1980;2(3):329-46
pubmed: 7403736
J Am Geriatr Soc. 2005 Dec;53(12):2170-2
pubmed: 16398904
PLoS Genet. 2017 Jul 5;13(7):e1006849
pubmed: 28678786
Neurobiol Aging. 1997 Jul-Aug;18(4):351-7
pubmed: 9330961
Ageing Res Rev. 2010 Jan;9(1):51-60
pubmed: 19619672
J Athl Train. 2007 Jul-Sep;42(3):333-42
pubmed: 18059987
J Neurosci. 2007 Mar 21;27(12):3090-7
pubmed: 17376970
Acta Neuropathol Commun. 2018 Jan 3;6(1):1
pubmed: 29298724
Neuroscience. 1995 Dec;69(3):691-8
pubmed: 8596639
J Exp Zool. 1975 Oct;194(1):175-88
pubmed: 1104753
Sleep. 1983;6(1):36-46
pubmed: 6844796
Sleep. 1988 Apr;11(2):210-9
pubmed: 3381061
Neurobiol Aging. 2022 May;113:118-130
pubmed: 35334439
J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9
pubmed: 22002422
Front Neurosci. 2019 May 29;13:529
pubmed: 31191227
Nat Med. 2020 Mar;26(3):379-386
pubmed: 32123385
Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
pubmed: 3088567
Nat Rev Neurosci. 2020 Jan;21(1):21-35
pubmed: 31780819
Alzheimers Dement. 2012 Jan;8(1):65-73
pubmed: 22047631
Biochem Soc Symp. 1976;(41):33-42
pubmed: 788719
Sci Rep. 2017 Apr 12;7:46359
pubmed: 28402338
Med Sci Sports Exerc. 2006 Nov;38(11):1926-31
pubmed: 17095925
JAMA Neurol. 2021 Aug 1;78(8):961-971
pubmed: 34180956
J Nucl Med. 2016 Oct;57(10):1599-1606
pubmed: 27230925
Psychophysiology. 1990 Sep;27(5):560-6
pubmed: 2274619
Ageing Res Rev. 2002 Sep;1(4):721-78
pubmed: 12208240
Brain Res. 1992 Sep 11;590(1-2):239-49
pubmed: 1330213
Front Neuroanat. 2019 Jun 06;13:57
pubmed: 31244617
Front Physiol. 2021 May 10;12:659973
pubmed: 34040543
Altern Med Rev. 2007 Mar;12(1):49-62
pubmed: 17397267
Biol Rhythm Res. 2007;38(4):275-325
pubmed: 23710111
J Nucl Med. 1998 May;39(5):904-11
pubmed: 9591599
Gerontology. 2012;58(4):289-95
pubmed: 22085834
Front Mol Neurosci. 2014 Mar 11;7:16
pubmed: 24653673
Biochem Soc Trans. 2012 Aug;40(4):711-5
pubmed: 22817721
Brain. 2016 May;139(Pt 5):1551-67
pubmed: 26962052
Neurobiol Aging. 2017 Feb;50:25-29
pubmed: 27838492
Arch Med Res. 2012 Nov;43(8):655-62
pubmed: 23142263
J Appl Physiol (1985). 2003 Dec;95(6):2598-603
pubmed: 14600165
Sci Rep. 2012;2:480
pubmed: 22761989
Sleep. 1991 Dec;14(6):540-5
pubmed: 1798888
Curr Med Chem. 2008;15(23):2321-8
pubmed: 18855662
J Neurosci. 2008 Nov 26;28(48):12798-807
pubmed: 19036972
Science. 2008 Feb 22;319(5866):1086-9
pubmed: 18202255
J Neural Transm (Vienna). 2005 Jun;112(6):813-38
pubmed: 15517432
Lancet Neurol. 2020 May;19(5):422-433
pubmed: 32333900
Mol Psychiatry. 2017 Feb;22(2):306-311
pubmed: 27021814
Brain Commun. 2020 Aug 19;2(2):fcaa132
pubmed: 33215083
Curr Opin Neurobiol. 2021 Aug;69:131-138
pubmed: 33892381
Acta Neuropathol. 2002 Jan;103(1):26-35
pubmed: 11837744
Br J Sports Med. 2007 Mar;41(3):126-33
pubmed: 17178778
J Nutr Health Aging. 2012 Oct;16(10):888-90
pubmed: 23208027
J Neurosci. 2004 Mar 10;24(10):2401-11
pubmed: 15014115
Annu Rev Physiol. 2019 Feb 10;81:285-308
pubmed: 30256726
Scand J Caring Sci. 2002 Jun;16(2):122-8
pubmed: 12000664
Sci Rep. 2019 Jan 29;9(1):832
pubmed: 30696859
Nat Med. 2020 Mar;26(3):398-407
pubmed: 32161412
J Biol Rhythms. 1998 Apr;13(2):123-31
pubmed: 9554574
Am J Physiol. 1994 Sep;267(3 Pt 2):R819-29
pubmed: 8092328
Comp Biochem Physiol. 1968 Dec;27(3):659-68
pubmed: 5710275
Sleep. 2020 Apr 15;43(4):
pubmed: 31702011
Alzheimers Res Ther. 2018 Jul 31;10(1):74
pubmed: 30064520
Annu Rev Pathol. 2019 Jan 24;14:239-261
pubmed: 30355155
Temperature (Austin). 2016 Apr 6;3(2):208-219
pubmed: 27857951
Brain. 2021 Sep 4;144(8):2284-2290
pubmed: 33742656