Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Gozes, Illana

doi:10.1007/s13167-017-0110-x

Cited by 10 publications

(5 citation statements)

References 48 publications

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“…Cerebrospinal fluid (CSF) Aβ42 and tau have been used to diagnose AD and monitor disease progression [8]. In the past decade, other biomarkers have been confirmed to further characterize the pathophysiological process of AD [9].…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease

Chen¹,

Therriault²,

Luo³

et al. 2021

J. Integr. Neurosci.

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Cerebrospinal fluid neurofilament light and plasma neurofilament light concentrations are elevated in patients with mild cognitive impairment and Alzheimer's disease. We investigated the clinical relevance of increased neurofilament light concentrations in mild cognitive impairment and Alzheimer's disease patients. In this study, 244 subjects were divided into cognitively normal control (n = 67), stable mild cognitive impairment (n = 52), progressive mild cognitive impairment (n = 68), and Alzheimer's disease (n = 57). Linear regression examined the relationships between neurofilament light levels in cerebrospinal fluid or plasma and the diagnostic group. The relationships between neurofilament light and other biomarkers were assessed by Spearman correlation. Linear mixed-effects models were used to test cerebrospinal fluid and plasma neurofilament light as predictors of Alzheimer's disease characteristics, including cognition, cortical glucose metabolism, and brain structure. Cerebrospinal fluid and plasma neurofilament light levels were significantly elevated in Alzheimer's disease. Still, the correlations between neurofilament light and other cerebrospinal fluid biomarkers within the diagnostic groups were often not statistically significant. In addition, the diagnostic accuracy of cerebrospinal fluid and plasma neurofilament light for progressive mild cognitive impairment and Alzheimer's disease was almost the same as that of cerebrospinal fluid total tau (T-tau). It is phosphorylated tau (Ptau) and high cerebrospinal fluid. Neurofilament light predicted conversion from mild cognitive impairment to Alzheimer's disease. A high neurofilament light is related to poor cognition, low cerebral metabolism, hippocampal atrophy, and ventricular enlargement caused by Alzheimer's disease. Our work further identifies cerebrospinal fluid neurofilament light and plasma neurofilament light as biomarkers of axonal degeneration in patients with mild cognitive impairment and Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease

Chen¹,

Therriault²,

Luo³

et al. 2021

J. Integr. Neurosci.

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“…Abundances of several CSF proteins have been approved as diagnostic or prognostic markers in clinical practice. For instance, total tau protein concentration, phospho-tau concentration and presence of 42 amino acid form of β-amyloid are indicative of Alzheimer´s disease [1]. Similarly, the appearance of oligoclonal immunoglobulin bands on electrophoretic gels of a CSF sample suggest the presence of multiple sclerosis [2].…”

Section: Introductionmentioning

confidence: 99%

Affinity depletion versus relative protein enrichment: a side-by-side comparison of two major strategies for increasing human cerebrospinal fluid proteome coverage

et al. 2019

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Cerebrospinal fluid (CSF) is in direct contact with the central nervous system. This makes human CSF an attractive source of potential biomarkers for neurologic diseases. Similarly to blood plasma, proteomic analysis of CSF is complicated by a high dynamic range of individual protein concentrations and by the presence of several highly abundant proteins. To deal with the abundant human CSF proteins, methods developed for blood plasma/serum are routinely used. Multiple affinity removal systems and protein enrichment of less abundant proteins using a combinatorial peptide ligand library are among the most frequent approaches. However, their relative impact on CSF proteome coverage has never been evaluated side-by-side in a single study. Therefore, we explored the effect of CSF depletion using MARS 14 cartridge and ProteoMiner ligand library on the number of CSF proteins identified in subsequent LC–MS/MS analysis. LC–MS/MS analysis of crude (non-treated) CSF provided roughly 500 identified proteins. Depletion of CSF by MARS 14 cartridge increased the number of identifications to nearly 800, while treatment of CSF using ProteoMiner enabled identification of 600 proteins. To explore the potential losses of CSF proteins during the depletion process, we also analyzed the “waste” fractions generated by both methods, i.e., proteins retained by the MARS 14 cartridge, and the molecules present in the flow-through fraction from ProteoMiner. More than 250 proteins were bound to MARS 14 cartridge, 100 of those were not identified in the corresponding depleted CSF. Similarly, analysis of the waste fraction in ProteoMiner workflow provided almost 70 unique proteins not found in the CSF depleted by the ligand library. Both depletion strategies significantly increased the number of identified CSF proteins compared to crude CSF. However, MARS 14 depletion provided a markedly higher number of identified proteins (773) compared to ProteoMiner (611). Further, we showed that CSF proteins are lost due to co-depletion (MARS 14) or exclusion (ProteoMiner) during the depletion process. This suggests that the routinely discarded “waste” fractions contain proteins of potential interest and should be included in CSF biomarker studies. Electronic supplementary material The online version of this article (10.1186/s12014-019-9229-1) contains supplementary material, which is available to authorized users.

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“…Based on the nature of the pathophysiology that each measures, the “A/T/N” system for biomarkers has been proposed, and Aβ is first, followed by tau, then neurodegeneration [ 3 ]. Over the past decade, inflammatory factors and other proteins have been proposed to further characterize the AD pathophysiological process [ 4 ]. It is important to study the ability of these biomarkers to make accurate diagnoses, which can permit for population enrichment of clinical trials [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

Zhang

Therriault

et al. 2018

Transl Neurodegener

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BackgroundVisinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer’s disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD.MethodsWe stratified 121 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD. Analysis of covariance (ANOVA) and chi-square analyses, Spearman correlation, and logistic regression models were performed to test the demographic, associations between biomarkers, and diagnostic accuracies, respectively. Linear mixed-effects models were used to evaluate the effects of CSF amyloid-β (Aβ) on above biomarkers within diagnostic groups, the combination of diagnostic group and Aβ status as predictor, and CSF biomarkers as predictors of AD features, including cognition measured by Mini–Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI).ResultsP-tau, VILIP-1, and YKL-40 were all predictors of AD diagnosis, but combinations of biomarkers did not improve the diagnostic accuracy (AUC 0.924 for p-tau, VILIP-1, and YKL-40) compared to p-tau (AUC 0.922). P-tau and VILIP-1 were highly correlated (r = 0.639, p < 0.001) and strongly associated with Aβ pathology across clinical stages of AD, while YKL-40 was correlated with Aβ pathology in CN and AD groups. VILIP-1 was associated with acceleration of cognitive decline, hippocampal atrophy, and expansion of ventricles in longitudinal analyses. YKL-40 was associated with hippocampal atrophy at baseline and follow-up, while p-tau was only associated with worsening WMH at baseline.ConclusionsCSF levels of p-tau, VILIP-1, and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD. Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration. These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD.Electronic supplementary materialThe online version of this article (10.1186/s40035-018-0127-7) contains supplementary material, which is available to authorized users.

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Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Cited by 10 publications

References 48 publications

Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease

Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease

Affinity depletion versus relative protein enrichment: a side-by-side comparison of two major strategies for increasing human cerebrospinal fluid proteome coverage

Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

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