Particular CSF sphingolipid patterns identify iNPH and AD patients

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by reversible neurological symptoms due to an impairment in cerebrospinal fluid (CSF) clearance. In these patients, cognitive functions are severely impaired, with a scenario similar to Alzheimer’s disease (AD), making the differential diagnosis difficult and highlighting the need of new markers. We analyzed the composition of sphingolipids (SLs) in serum, by combining a single phase extraction with a high-performance thin-layer chromatography (HPTLC) primuline-profiling, and, in CSF, by MALDI profiling and LC-MS. Ceramides and sphingomyelins (SMs) were similar in serum of iNPH and AD patients compared to healthy controls, whereas, in CSF, MALDI profiling indicated that: 1) SM C24:1 is significantly decreased in AD compared to iNPH patients and controls (Kruskal-Wallis p-value < 0.00001); 2) phosphatidylcholine (PC) 36:2 is increased in iNPH patients (p-value < 0.001). LC-MS identified an increasing trend of Cer C24:0 and of a set of SMs in patients with AD, a significant decrease of sphingosine-1-phosphate (S1P) (t-test p-value 0.0325) and an increase of glucosylceramide (GlcCer) C24:0 (p-value 0.0037) in AD compared to iNPH patients. In conclusion CSF PC 36:2, SM C24:1, S1P, and GlcCer can contribute to improve the differential diagnosis of patients with iNPH or AD and foster preventive therapeutic strategies in the early phase of the disease.

Alteration of Sphingolipids in Biofluids: Implications for Neurodegenerative Diseases

“…The higher levels of ceramide species in plasma of AD patients is in accordance with a previous study that observed higher content of total ceramides in CSF of AD patients compared with the control group [52]. Likewise, a recent work that evaluated serum SL by high-performance thin layer chromatography (HPTLC)-densitometry observed higher long and short chain ceramides in AD compared to controls [53]. The consistency of results observed in plasma, serum and CSF of AD patients supports the idea of a general biofluid increase in ceramide levels at least for this disease.…”

“…Moreover, depending on the technique used to separate the molecules it is possible to identify the sphingoid base of each SM species, and therefore it is difficult to compare results from different studies at species level [46]. Table 3 shows the results obtained in two studies with AD patients [47,53], and single studies of PD [54], MS [55], and amyotrophic lateral sclerosis (ALS) [56]. SM species were found decreased in AD, PD and MS compared to controls (Table 3).…”

“…This SL is a component of myelin sheath and may be reflecting its breakdown as part of motor neurons death [58]. Increased plasma levels of short chain SM were reported in AD compared to control subjects when evaluated by HPTLC, a result that was not corroborated in CSF using MALDI/MS-MS in the same study [53]. The comparison of results from different body fluids and the use of two different analytical techniques make it difficult to identify the reason of the discrepancy.…”

Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer’s disease and vascular cognitive impairment

“…One of the important functions of S1P is in modulating vascular biology; for example, it has been demonstrated that S1P is involved in endothelial barrier integrity, and vascular smooth muscle function [ 51 , 65 ]. Peripheral and CSF S1P has also been found to be altered in stenosis and stroke, a key event prior to onset of VCI [ 66 ] as well as in AD [ 67 ]. It is likely that peripheral S1P may also be affecting the CNS in indirect ways.…”

Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults

“…Sera samples were extracted according to the procedure of Alshehry et al . 51 , with minor modifications, as already described in 52 .…”