The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

Kang, Ju‐Hee; Korecka, Magdalena; Figurski, Michal; Toledo, Jon B.; Blennow, Kaj; Zetterberg, Henrik; Waligórska, Teresa; Brylska, Magdalena; Fields, Leona; Shah, Nirali; Soares, Holly; Dean, Robert A.; Vanderstichele, Hugo; Petersen, Ronald C.; Aisen, Paul S.; Saykin, Andrew J.; Weiner, Michael W.; Trojanowski, John Q.; Shaw, Leslie M.

doi:10.1016/j.jalz.2015.05.003

Cited by 88 publications

(92 citation statements)

References 128 publications

(152 reference statements)

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“…Aβ 42 , t-tau, and p-tau 181 were measured using the multiplex xMAP Luminex platform (Luminex Corp, Austin, TX) with Innogenetics (INNO-BIA AlzBio3; Ghent, Belgium) immunoassay kit–based reagents, as previously described[31, 32]. The data was obtained from the ADNI database (http://adni.loni.usc.edu).…”

Section: Methodsmentioning

confidence: 99%

A Longitudinal Study of Total and Phosphorylated α-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer’s Disease and Mild Cognitive Impairment

Wang

Stewart

Toledo

et al. 2018

JAD

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Alzheimer’s disease (AD) features a dynamic sequence of amyloid deposition, neurodegeneration, and cognitive impairment. A significant fraction of AD brains also displays Lewy body pathology, suggesting that addition of classically Parkinson’s disease-related proteins to the AD biomarker panel may be of value. To determine whether addition of cerebrospinal fluid (CSF) total α-synuclein and its form phosphorylated at S129 (pS129) to the AD biomarker panel [Amyloid-β1-42 (Aβ42), tau, and phosphorylated tau (p-tau181)] improves its performance, we examined CSF samples collected longitudinally up to 7 years as part of the Alzheimer’s Disease Neuroimaging Initiative. From 87 AD, 177 mild cognitive impairment (MCI), and 104 age-matched healthy controls, 792 baseline and longitudinal CSF samples were tested for total α-synuclein, pS129, Aβ42, tau, and p-tau181. pS129, but not total α-synuclein, was weakly associated with diagnosis at baseline when t-tau/Aβ42 was included in the statistical model (β=0.0026, p=0.041, 95% CI [(0.0001)–(0.005)]). CSF α-synuclein predicted Alzheimer’s Disease Assessment Scale-Cognitive (β=−0.59, p=0.0015, 95% CI [(−0.96)–(−0.23)]), memory (β=0.4, p=0.00025, 95% CI [(0.16)–(0.59)]) and executive (0.62, <0.0001, 95% CI [(0.31)–(0.93)]) function composite scores, and progression from MCI to AD (β=0.019, p=0.0011, 95% CI [(0.002)–(0.20)]). pS129 was associated with executive function (β=−2.55, p=0.0085, 95% CI [(−4.45)–(−0.66)]). Lower values in the mismatch between α-synuclein and p-tau181 predicted faster cognitive decline (β=0.64, p=0.0012, 95% CI [(0.48)–(0.84)]). Longitudinal biomarker changes did not differ between groups, and may not reflect AD progression. The α-synuclein-p-tau181-Mismatch could better predict longitudinal cognitive changes than classical AD markers alone, and its pathological correlates should be investigated further.

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Section: Methodsmentioning

confidence: 99%

A Longitudinal Study of Total and Phosphorylated α-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer’s Disease and Mild Cognitive Impairment

Wang

Stewart

Toledo

et al. 2018

JAD

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“…[54]. Thirdly, it will directly address the lack of reliability of Aβ and tau phenotyping through the standardization of different amyloid PET tracers in the ‘Centiloid project’, and the development of new immunoassay platforms and mass spectroscopy techniques to improve the reliability of CSF analysis of Aβ and tau as well as assess the utility of CSF synaptic protein biomarkers such as neurogranin [55]. Lastly, in conjunction with the Brain Health Registry (BHR; www.brainhealthregistry.org [56]), it will implement web-based methods for recruitment and characterization of subjects to overcome the problems of slow recruitment, and high trial costs due to high “screen fails”.…”

Section: Introductionmentioning

confidence: 99%

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Weiner

Veitch

Aisen

et al. 2016

Alzheimer's & Dementia

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277

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INTRODUCTION The overall goal of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer’s disease (AD) clinical trials. ADNI-3, beginning August 1, 2016, is a five year renewal of the current ADNI-2 study. METHODS ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment (MCI) and AD using innovative technologies such as tau imaging, magnetic resonance imaging (MRI) sequences for connectivity analyses, and a highly-automated immunoassay platform and mass spectroscopy approach for CSF biomarker analysis. A Systems Biology/Pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography (PET) scanning will be standardized using by the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. RESULTS Multi-modal analyses will provide insight into AD pathophysiology and disease progression. DISCUSSION ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.

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“…Using human CSF samples and adopting targeted approach, Shi et al [72] proposed a panel consisting of five peptides/ proteins such as osteopontin (SPP1), prolow-density lipoprotein receptor-related protein 1 (LRP1), macrophage colony-stimulating factor 1 receptor (CSF1R), ephrin type-A receptor 4 (EPHA4), and metalloproteinase inhibitor 1 (TIMP1) are biomarkers of PD or AD. Alzheimer's Disease Neuroimaging Initiative (ADNI) biomarker core progress has been reviewed by Kang et al [73].…”

Section: Proteomic Biomarkers Of Dementiamentioning

confidence: 99%

Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

Adav¹,

Sze²

2016

Update on Dementia

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Dementia is a major public health burden, and the World Health Organization has identified this disorder as a major public health priority. There are limited treatment options due to poor understanding of key mechanism of dementia pathogenesis. Dementia has been regarded as a proteinopathy in which alterations of brain protein structure and function are the key features of the disorder. Proteinopathy can be triggered by degenerative protein modifications (DPMs), misfolding, aggregation, and deposition of the malformed proteins. Despite the clinical significance of alteration in protein abundances, DPMs, protein misfolding, and aggregation, the molecular mechanism that promotes these changes remains inadequately understood, mostly due to technical challenges. Proteomic is a powerful, sensitive, and advanced tool to study the progressive brain tissue damage that critically dysregulates key enzymes, accumulates modified proteins, and causes protein misfolding and aggregation, resulting in cognitive decline and dementia. The proteomic profiling of protein abundances and correlating DPMs with protein misfolding and aggregation have potential to elucidate underlying molecular mechanism of the disease. This chapter summarizes the recent proteomic developments for studying brain proteome, DPMs, and protein aggregation mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues.

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The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

Cited by 88 publications

References 128 publications

A Longitudinal Study of Total and Phosphorylated α-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer’s Disease and Mild Cognitive Impairment

A Longitudinal Study of Total and Phosphorylated α-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer’s Disease and Mild Cognitive Impairment

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

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