Association between lower body temperature and increased tau pathology in cognitively normal older adults
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122001401 |
| _version_ | 1818465789743726592 |
|---|---|
| author | Esther M. Blessing Ankit Parekh Rebecca A. Betensky James Babb Natalie Saba Ludovic Debure Andrew W. Varga Indu Ayappa David M. Rapoport Tracy A. Butler Mony J. de Leon Thomas Wisniewski Brian J. Lopresti Ricardo S. Osorio |
| author_facet | Esther M. Blessing Ankit Parekh Rebecca A. Betensky James Babb Natalie Saba Ludovic Debure Andrew W. Varga Indu Ayappa David M. Rapoport Tracy A. Butler Mony J. de Leon Thomas Wisniewski Brian J. Lopresti Ricardo S. Osorio |
| author_sort | Esther M. Blessing |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:50:21Z |
| format | Article |
| id | doaj.art-dccf07f08d5e400ab5e17b4071c2f542 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-13T20:50:21Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-dccf07f08d5e400ab5e17b4071c2f5422022-12-22T02:30:32ZengElsevierNeurobiology of Disease1095-953X2022-09-01171105748Association between lower body temperature and increased tau pathology in cognitively normal older adultsEsther M. Blessing0Ankit Parekh1Rebecca A. Betensky2James Babb3Natalie Saba4Ludovic Debure5Andrew W. Varga6Indu Ayappa7David M. Rapoport8Tracy A. Butler9Mony J. de Leon10Thomas Wisniewski11Brian J. Lopresti12Ricardo S. Osorio13Department of Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, United States of America; Corresponding author.Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States of AmericaDepartment of NYU School of Global Public Health, New York, NY 10016, United States of AmericaAlzheimer's Disease Research Center, Department of Neurology, NYU Grossman School of Medicine, New York, NY 10016, United States of AmericaDepartment of Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, United States of AmericaAlzheimer's Disease Research Center, Department of Neurology, NYU Grossman School of Medicine, New York, NY 10016, United States of AmericaMount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States of AmericaMount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States of AmericaMount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States of AmericaDepartment of Neurology, Weill Cornell Medicine, New York, NY 10065, United States of AmericaDepartment of Neurology, Weill Cornell Medicine, New York, NY 10065, United States of AmericaAlzheimer's Disease Research Center, Department of Neurology, NYU Grossman School of Medicine, New York, NY 10016, United States of AmericaDepartment of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, United States of AmericaDepartment of Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, United States of America; Alzheimer's Disease Research Center, Department of Neurology, NYU Grossman School of Medicine, New York, NY 10016, United States of AmericaBackground: 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.http://www.sciencedirect.com/science/article/pii/S0969996122001401TauPhosphorylationBody temperatureAgingAlzheimer's diseaseNeurofibrillary tangle |
| spellingShingle | Esther M. Blessing Ankit Parekh Rebecca A. Betensky James Babb Natalie Saba Ludovic Debure Andrew W. Varga Indu Ayappa David M. Rapoport Tracy A. Butler Mony J. de Leon Thomas Wisniewski Brian J. Lopresti Ricardo S. Osorio Association between lower body temperature and increased tau pathology in cognitively normal older adults Neurobiology of Disease Tau Phosphorylation Body temperature Aging Alzheimer's disease Neurofibrillary tangle |
| title | Association between lower body temperature and increased tau pathology in cognitively normal older adults |
| title_full | Association between lower body temperature and increased tau pathology in cognitively normal older adults |
| title_fullStr | Association between lower body temperature and increased tau pathology in cognitively normal older adults |
| title_full_unstemmed | Association between lower body temperature and increased tau pathology in cognitively normal older adults |
| title_short | Association between lower body temperature and increased tau pathology in cognitively normal older adults |
| title_sort | association between lower body temperature and increased tau pathology in cognitively normal older adults |
| topic | Tau Phosphorylation Body temperature Aging Alzheimer's disease Neurofibrillary tangle |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122001401 |
| work_keys_str_mv | AT esthermblessing associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT ankitparekh associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT rebeccaabetensky associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT jamesbabb associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT nataliesaba associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT ludovicdebure associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT andrewwvarga associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT induayappa associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT davidmrapoport associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT tracyabutler associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT monyjdeleon associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT thomaswisniewski associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT brianjlopresti associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults AT ricardososorio associationbetweenlowerbodytemperatureandincreasedtaupathologyincognitivelynormalolderadults |