Dataset Information

Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?

ABSTRACT: Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease, which is currently diagnosed via clinical symptoms and nonspecific biomarkers (such as Aβ_1-42, t-Tau, and p-Tau) measured in cerebrospinal fluid (CSF), which alone do not provide sufficient insights into disease progression. In this pilot study, these biomarkers were complemented with small-molecule analysis using non-target high-resolution mass spectrometry coupled with liquid chromatography (LC) on the CSF of three groups: AD, mild cognitive impairment (MCI) due to AD, and a non-demented (ND) control group. An open-source cheminformatics pipeline based on MS-DIAL and patRoon was enhanced using CSF- and AD-specific suspect lists to assist in data interpretation. Chemical Similarity Enrichment Analysis revealed a significant increase of hydroxybutyrates in AD, including 3-hydroxybutanoic acid, which was found at higher levels in AD compared to MCI and ND. Furthermore, a highly sensitive target LC-MS method was used to quantify 35 bile acids (BAs) in the CSF, revealing several statistically significant differences including higher dehydrolithocholic acid levels and decreased conjugated BA levels in AD. This work provides several promising small-molecule hypotheses that could be used to help track the progression of AD in CSF samples.

SUBMITTER: Talavera Andujar B

PROVIDER: S-EPMC10919072 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?

Talavera Andújar Begoña B Mary Arnaud A Venegas Carmen C Cheng Tiejun T Zaslavsky Leonid L Bolton Evan E EE Heneka Michael T MT Schymanski Emma L EL

Environmental science & technology 20240219 9

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease, which is currently diagnosed via clinical symptoms and nonspecific biomarkers (such as Aβ<sub>1-42</sub>, t-Tau, and p-Tau) measured in cerebrospinal fluid (CSF), which alone do not provide sufficient insights into disease progression. In this pilot study, these biomarkers were complemented with small-molecule analysis using non-target high-resolution mass spectrometry coupled with liquid chromatography (LC) on t ...[more]

PMID: 38373301

Similar Datasets

Project description:BackgroundAlzheimer's disease (AD) biomarkers are emerging as critically important for disease detection and monitoring. Most biomarkers are obtained through invasive, resource-intense procedures. A cognitive marker, intra-individual cognitive variability (IICV) may provide an alternative or adjunct marker of disease risk for individuals unable or disinclined to undergo lumbar puncture.ObjectiveTo contrast risk of incident AD and mild cognitive impairment (MCI) associated with IICV to risk associated with well-established biomarkers: cerebrospinal fluid (CSF) phosphorylated tau protein (p-tau181) and amyloid-β 42 (Aβ42) peptide.MethodsDispersion in cognitive performance, IICV, was estimated with a published algorithm, and included Trail Making Test A and B, Rey Auditory Verbal Learning Test (RAVLT), and the American National Adult Reading Test (ANART). CSF biomarkers were expressed as a ratio: p-tau181/Aβ42, wherein high values signified pathognomonic profiles. Logistic regression models included longitudinal data from 349 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who completed lumbar puncture. All subjects were cognitively healthy (n = 105) or diagnosed with MCI (n = 244) at baseline. We examined odds of conversion associated with baseline elevations in IICV and/or ratio of CSF p-tau181/Aβ42.ResultsWhen included in models alone or in combination with CSF p-tau181/Aβ42, one standard IICV unit higher was associated with an estimated odds ratio for incident AD or MCI of 2.81 (95% CI: 1.83-4.33) in the most inclusive sample, and an odds ratio of 3.41 (95% CI: 2.03-5.73) when restricted to participants with MCI. Iterative analyses suggested that IICV independently improved model fit even when individual index components were included in comparative models.ConclusionsThese analyses provide preliminary support for IICV as a marker of incident AD and MCI. This easily-disseminated, non-invasive marker compared favorably to well-established CSF biomarkers.

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder with clinical, biological, and pathological features occurring along a continuum from normal to end-stage disease. Currently, the diagnosis of AD depends on clinical assessments and post-mortem neuropathology, which is unbenefited early diagnosis and progressive monitoring. In recent years, clinical studies have reported that the level of cerebrospinal fluid (CSF) and blood neurogranin (Ng) are closely related to the occurrence and subsequent progression of AD. Therefore, the study used meta-analysis to identify the CSF and blood Ng levels for the development of diagnosis biomarker of patients with AD and mild cognitive impairment (MCI). We searched the Pubmed, Embase, Cochrane Library, and Web of Science databases. A total of 24 articles eligible for inclusion and exclusion criteria were assessed, including 4661 individuals, consisting of 1518 AD patients, 1501 MCI patients, and 1642 healthy control subjects. The level of CSF Ng significantly increased in patients with AD and MCI compared with healthy control subjects (SMD: 0.84 [95% CI: 0.70-0.98], P < 0.001; SMD: 0.53 [95% CI: 0.40-0.66], P = 0.008), and higher in AD patients than in MCI patients (SMD: 0.18 [95% CI: 0.07-0.30], P = 0.002), and CSF Ng level of patients with MCI-AD who progressed from MCI to AD was significantly higher than that of patients with stable MCI (sMCI) (SMD: 0.71 [95% CI: 0.25-1.16], P = 0.002). Moreover, the concentration of Ng in blood plasma exosomes of patients with AD and MCI was lower than that of healthy control subjects (SMD: -6.657 [95% CI: -10.558 to -2.755], P = 0.001; and SMD: -3.64 [95% CI: -6.50 to -0.78], P = 0.013), and which in patients with AD and MCI-AD were also lower than those in patients with sMCI (P < 0.001). Furthermore, regression analysis showed a negative relationship between MMSE scores and CSF Ng levels in MCI patients (slope = -0.249 [95% CI: -0.003 to -0.495], P = 0.047). Therefore, the Ng levels increased in CSF, but decreased in blood plasma exosomes of patients with AD and MCI-AD, and highly associated with cognitive declines. These findings provide the clinical evidence that CSF and blood exosomes Ng can be used as a cognitive biomarker for AD and MCI-AD, and further studies are needed to define the specific range of Ng values for diagnosis at the different stages of AD.

Dataset Information

Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?

Publications

Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets