Dataset Information

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study.

ABSTRACT:

Introduction

Biomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (A?42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD. Histological studies and animal models indicate that amyloid beta 1-43 (A?43) aggregates early, and may play a role in the pathological process of AD. We have examined levels of CSF A?43 in a 2-year longitudinal study of aMCI and early AD.

Materials and methods

Cerebrospinal fluid was collected at baseline, and after one and 2 years from patients with AD (n = 19), and patients with aMCI (n = 42). Of these, 21 progressed to AD during the 2 years of study, whereas 21 did not. Controls (n = 32) were lumbar punctured at baseline only. CSF analyses of A?43, A?42, and total tau were carried out with ELISA.

Results

At baseline, CSF A?43, CSF A?42 and ratios with total tau could be used to separate controls from all three patient groups. CSF A?43, but not A?42, could separate patients with aMCI who progressed to AD during the 2 years of follow-up, from those that did not. The CSF total tau/A?43 ratio had a slightly but significantly larger area under the receiver operating characteristic curve when compared to the CSF total tau/A?42 ratio. CSF A?43 levels, but not A?42 levels, decreased from baseline to 2 years in the AD group.

Discussion and conclusion

CSF A?43 was demonstrated to be significantly reduced in patients already by the time that aMCI or AD was diagnosed, compared to controls, and this change must have occurred during the preclinical period. Since our results suggested that CSF A?43 distinguishes between subgroups of patients with aMCI better than CSF A?42, it may prove to be a useful additional biomarker for identifying aMCI patients at greatest risk of AD.

SUBMITTER: Lauridsen C

PROVIDER: S-EPMC4772322 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study.

Lauridsen Camilla C Sando Sigrid B SB Shabnam Adiba A Møller Ina I Berge Guro G Grøntvedt Gøril R GR Bakken Inger J IJ Salvesen Øyvind Ø Bråthen Geir G White Linda R LR

Frontiers in aging neuroscience 20160301

<h4>Introduction</h4>Biomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (Aβ42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD. Histological studies and animal models indicate tha ...[more]

PMID: 26973507

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Project description:BACKGROUND:Alzheimer'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. OBJECTIVE:To 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-? 42 (A?42) peptide. METHODS:Dispersion 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/A?42, 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/A?42. RESULTS:When included in models alone or in combination with CSF p-tau181/A?42, 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. CONCLUSIONS:These 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.

Dataset Information

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study.

Introduction

Materials and methods

Results

Discussion and conclusion

Publications

Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study.

Similar Datasets

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