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Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

ABSTRACT: High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na⁺]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na⁺] from hypertensive and normotensive human subjects with family histories of Alzheimer's disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na⁺] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na⁺] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na⁺], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na⁺] and BP but showed no correlation between plasma [Na⁺] and BP. In sum, CSF [Na⁺] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na⁺] in chronic hypertension in humans.

SUBMITTER: Souza LAC

PROVIDER: S-EPMC7099411 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

Souza Lucas A C LAC Trebak Fatima F Kumar Veena V Satou Ryousuke R Kehoe Patrick G PG Yang Wei W Wharton Whitney W Feng Earley Yumei Y

Physiological genomics 20200121 3

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na<sup>+</sup>]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na<sup ...[more]

PMID: 31961762

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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-?1-42. 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-?1-42 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-? 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-?1-42 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 ?4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-?1-42 values and APOE ?2 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-?1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-?1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Dataset Information

Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

Publications

Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

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