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Войти в исследования JAMA psychiatry · 2020
Cortical Proteins Associated With Cognitive Resilience in Community-Dwelling Older Persons.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Yu Lei, Tasaki Shinya, Schneider Julie A, Arfanakis Konstantinos, Duong Duc M, Wingo Aliza P, Wingo Thomas S, Kearns Nicola, Thatcher Gregory R J, Seyfried Nicholas T, Levey Allan I, De Jager Philip L, Bennett David A
Аннотация
IMPORTANCE: Identifying genes and proteins for cognitive resilience (ie, targets that may be associated with slowing or preventing cognitive decline regardless of the presence, number, or combination of common neuropathologic conditions) provides a complementary approach to developing novel therapeutics for the treatment and prevention of Alzheimer disease and related dementias.
OBJECTIVE: To identify proteins associated with cognitive resilience via a proteome-wide association study of the human dorsolateral prefrontal cortex.
DESIGN, SETTING, AND PARTICIPANTS: This study used data from 391 community-dwelling older persons who participated in the Religious Orders Study and the Rush Memory and Aging Project. The Religious Orders Study began enrollment January 1, 1994, and the Rush Memory and Aging Project began enrollment September 1, 1997, and data were collected and analyzed through October 23, 2019.
EXPOSURES: Participants had undergone annual detailed clinical examinations, postmortem evaluations, and tandem mass tag proteomics analyses.
MAIN OUTCOMES AND MEASURES: The outcome of cognitive resilience was defined as a longitudinal change in cognition over time after controlling for common age-related neuropathologic indices, including Alzheimer disease, Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, infarcts, and vessel diseases. More than 8000 high abundance proteins were quantified from frozen dorsolateral prefrontal cortex tissue using tandem mass tag and liquid chromatography-mass spectrometry.
RESULTS: There were 391 participants (273 women); their mean (SD) age was 79.7 (6.7) years at baseline and 89.2 (6.5) years at death. Eight cortical proteins were identified in association with cognitive resilience: a higher level of NRN1 (estimate, 0.140; SE, 0.024; P = 7.35 × 10-9), ACTN4 (estimate, 0.321; SE, 0.065; P = 9.94 × 10-7), EPHX4 (estimate, 0.198; SE, 0.042; P = 2.13 × 10-6), RPH3A (estimate, 0.148; SE, 0.031; P = 2.58 × 10-6), SGTB (estimate, 0.211; SE, 0.045; P = 3.28 × 10-6), CPLX1 (estimate, 0.136; SE, 0.029; P = 4.06 × 10-6), and SH3GL1 (estimate, 0.179; SE, 0.039; P = 4.21 × 10-6) and a lower level of UBA1 (estimate, -0.366; SE, 0.076; P = 1.43 × 10-6) were associated with greater resilience.
CONCLUSIONS AND RELEVANCE: These protein signals may represent novel targets for the maintenance of cognition in old age.
OBJECTIVE: To identify proteins associated with cognitive resilience via a proteome-wide association study of the human dorsolateral prefrontal cortex.
DESIGN, SETTING, AND PARTICIPANTS: This study used data from 391 community-dwelling older persons who participated in the Religious Orders Study and the Rush Memory and Aging Project. The Religious Orders Study began enrollment January 1, 1994, and the Rush Memory and Aging Project began enrollment September 1, 1997, and data were collected and analyzed through October 23, 2019.
EXPOSURES: Participants had undergone annual detailed clinical examinations, postmortem evaluations, and tandem mass tag proteomics analyses.
MAIN OUTCOMES AND MEASURES: The outcome of cognitive resilience was defined as a longitudinal change in cognition over time after controlling for common age-related neuropathologic indices, including Alzheimer disease, Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, infarcts, and vessel diseases. More than 8000 high abundance proteins were quantified from frozen dorsolateral prefrontal cortex tissue using tandem mass tag and liquid chromatography-mass spectrometry.
RESULTS: There were 391 participants (273 women); their mean (SD) age was 79.7 (6.7) years at baseline and 89.2 (6.5) years at death. Eight cortical proteins were identified in association with cognitive resilience: a higher level of NRN1 (estimate, 0.140; SE, 0.024; P = 7.35 × 10-9), ACTN4 (estimate, 0.321; SE, 0.065; P = 9.94 × 10-7), EPHX4 (estimate, 0.198; SE, 0.042; P = 2.13 × 10-6), RPH3A (estimate, 0.148; SE, 0.031; P = 2.58 × 10-6), SGTB (estimate, 0.211; SE, 0.045; P = 3.28 × 10-6), CPLX1 (estimate, 0.136; SE, 0.029; P = 4.06 × 10-6), and SH3GL1 (estimate, 0.179; SE, 0.039; P = 4.21 × 10-6) and a lower level of UBA1 (estimate, -0.366; SE, 0.076; P = 1.43 × 10-6) were associated with greater resilience.
CONCLUSIONS AND RELEVANCE: These protein signals may represent novel targets for the maintenance of cognition in old age.
Предметные рубрики MeSH
ActininAdaptation, PsychologicalAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAgedAged, 80 and overCognitive DysfunctionEpoxide HydrolasesFemaleGPI-Linked ProteinsHumansIndependent LivingIntracellular Signaling Peptides and ProteinsMaleMolecular ChaperonesNerve Tissue ProteinsNeuropeptidesProteinsUbiquitin-Activating EnzymesVesicular Transport ProteinsRabphilin-3A