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.

What can 7T sodium MRI tell us about cellular energy depletion and neurotransmission in Alzheimer's disease?

“…Our study therefore points at a TSC imbalance accompanying the neurodegenerative process in AD in vivo. This finding confirms observations from post mortem studies 18,26 and the recent detection of sodium increases in AD patients and subjects at risk 19,20 . Interestingly, TSC can be highly discriminative between control subjects and only mildly affected patients in temporal regions such as the fusiform gyrus and is predictive for cognitive state.…”

“…This finding confirms observations from post mortem studies 18,26 and the recent detection of sodium increases in AD patients and subjects at risk. 19,20 Interestingly, TSC can be highly discriminative between control subjects and only mildly affected patients in temporal regions such as the fusiform gyrus and is predictive for cognitive state. TSC might therefore serve as a noninvasive and powerful marker of brain dysfunction even in early stages of the disease and could therefore be valuable, for example, as an outcome parameter for intervention trials.…”

“…In the context of AD, baseline studies have indeed shown a close interplay between the pathological hallmarks of AD, that is, amyloid beta (Aβ) deposits and tau tangles with the NKA in disease models 13–16 . Correspondingly, sodium and potassium concentration imbalances have been detected in post mortem brain tissue, and increased sodium concentrations have also been found in blood plasma of AD patients and in cerebrospinal fluid (CSF) of those at risk 17–20 …”

“…[13][14][15][16] Correspondingly, sodium and potassium concentration imbalances have been detected in post mortem brain tissue, and increased sodium concentrations have also been found in blood plasma of AD patients and in cerebrospinal fluid (CSF) of those at risk. [17][18][19][20] These findings point to the hypothesis that local sodium concentration changes detected in vivo by 23 Na-MRI might be useful as an early marker of neuronal dysfunction in AD, which could be associated with cognitive decline, and to investigate the crucial interplay between metabolic deficiency as a potential consequence of energy deficits and AD-related amyloid and tau pathologies. This type of imaging goes beyond the characteristic volumetric alterations of brain regions in AD pathology and could point to a more substantial hypothesis of failed neurotransmission as the basis of clinical implications.…”

3T sodium MR imaging in Alzheimer’s disease shows stage-dependent sodium increase influenced by age and local brain volume

“…We did not choose e.g. the ventricles, since CSF sodium values have also recently been detected to change in AD-pathology and those at risk for it ( Babić Leko et al, 2021 , Souza et al, 2020 ).…”