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Diurnal variations in salivary protein carbonyl levels in normal and cognitively impaired human subjects.

ABSTRACT: Oxidative stress has been documented in tissues and biofluids of subjects with sporadic Alzheimer disease (AD) and mild cognitive impairment (MCI). The aim of this study was to determine whether (a) salivary protein carbonyls are elevated in AD and MCI subjects, (b) salivary protein carbonyl contents in these groups exhibit diurnal variation, and (c) apolipoprotein E epsilon 4 (apoE epsilon 4) carrier status impacts salivary carbonyl concentrations or rhythmicity in the AD and MCI cohorts. Unstimulated saliva was collected at fixed intervals between 8 AM: and 10 PM: from 15 AD subject , 21 MCI subjects, and 30 cognitively-intact controls. Salivary protein carbonyl concentrations were measured by ELISA. ApoE genotyping was performed on the AD and MCI individuals. For all groups, mean protein carbonyl contents were significantly elevated at 2 PM: relative to other time points surveyed. Mean salivary protein carbonyl concentrations did not differ among the diagnostic groups. ApoE epsilon 4 carriers exhibited less temporal variation in salivary protein carbonyls relative to noncarriers. Thus, protein carbonyl content exhibits diurnal variation in adult human saliva. ApoE epsilon 4 carrier status may impact oropharyngeal disease expression by attenuating the inherent diurnal variability in salivary redox homeostasis. Salivary protein carbonyls do not differentiate AD and MCI from normal individuals. In conclusion, oxidative stress has been documented in tissues and biofluids of subjects with sporadic AD and MCI. This article demonstrates that levels of protein carbonyls, a marker of oxidative stress, exhibit robust diurnal variation in the saliva of normal elderly, MCI, and AD subjects. Apolipoprotein E epsilon 4 allele carrier status may attenuate this temporal variability in salivary redox homeostasis and thereby impact the natural history of oropharyngeal diseases.

SUBMITTER: Su H

PROVIDER: S-EPMC2276593 | biostudies-other | 2008 Mar

REPOSITORIES: biostudies-other

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Project description:In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Project description:BackgroundIn people with cognitive impairment, loss of social interactions has a major impact on well-being. Therefore, patients would benefit from early detection of symptoms of social withdrawal. Current measurement techniques such as questionnaires are subjective and rely on recall, in contradiction to smartphone apps, which measure social behavior passively and objectively.ObjectiveThis study uses the remote monitoring smartphone app Behapp to assess social behavior, and aims to investigate (1) the association between social behavior, demographic characteristics, and neuropsychiatric symptoms in cognitively normal (CN) older adults, and (2) if social behavior is altered in cognitively impaired (CI) participants. In addition, we explored in a subset of individuals the association between Behapp outcomes and neuropsychiatric symptoms.MethodsCN, subjective cognitive decline (SCD), and CI older adults installed the Behapp app on their own Android smartphone for 7 to 42 days. CI participants had a clinical diagnosis of mild cognitive impairment (MCI) or Alzheimer-type dementia. The app continuously measured communication events, app use and location. Neuropsychiatric Inventory (NPI) total scores were available for 20 SCD and 22 CI participants. Linear models were used to assess group differences on Behapp outcomes and to assess the association of Behapp outcomes with the NPI.ResultsWe included CN (n=209), SCD (n=55) and CI (n=22) participants. Older cognitively normal participants called less frequently and made less use of apps (P<.05). No sex effects were found. Compared to the CN and SCD groups, CI individuals called less unique contacts (β=-0.7 [SE 0.29], P=.049) and contacted the same contacts relatively more often (β=0.8 [SE 0.25], P=.004). They also made less use of apps (β=-0.83 [SE 0.25], P=.004). Higher total NPI scores were associated with further traveling (β=0.042 [SE 0.015], P=.03).ConclusionsCI individuals show reduced social activity, especially those activities that are related to repeated and unique behavior, as measured by the smartphone app Behapp. Neuropsychiatric symptoms seemed only marginally associated with social behavior as measured with Behapp. This research shows that the Behapp app is able to objectively and passively measure altered social behavior in a cognitively impaired population.

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Diurnal variations in salivary protein carbonyl levels in normal and cognitively impaired human subjects.

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