Molecular Markers of Amnestic Mild Cognitive Impairment among Mexican Americans

Edwards, Melissa; Hall, James; Williams, Benjamin J.; Johnson, Leigh; O’Bryant, Sid

doi:10.3233/jad-150553

Cited by 16 publications

(15 citation statements)

References 43 publications

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“…There are two primary results when examining the proteomic profile variable relative importance plots (Table 3). First, the proteomic profile of MCI among Mexican Americans appears to include a heavy inflammatory component, which is consistent with our recent work specifically examining a proteomic profile of amnestic MCI (Edwards et al, 2016). Secondly, the presence of diabetes (with or without depression) introduces higher rankings of metabolic markers in the profile (e.g.…”

Section: Resultssupporting

confidence: 87%

“…The AD algorithm consists of 21 proteins and has been validated across platforms, species, and tissue type. Additionally, this 21-protein AD algorithm retains excellent diagnostic accuracy in detecting MCI and AD among Mexican Americans (Edwards et al, 2016). The proteins included in the algorithm are as follows: fatty acid-binding protein (FABP), β2 microglobulin, pancreatic polypeptide (PPY), macrophage inflammatory protein-1α, CRP, soluble vascular cell adhesion molecule-1 (sVCAM-1), thrombopoietin, α2 macroglobulin, eotaxin 3, tumor necrosis factor-alpha (TNF-α), tenascin C (TNC), interleukin-5 (IL-5), IL-6, IL-7, IL-10, IL-18, I309, Factor VII, thymus and activation-regulated chemokine (TARC), serum amyloid A (SAA), and soluble intercellular cell adhesion molecule-1 (sICAM-1).…”

Section: Blood Collection and Biomarker Analysismentioning

confidence: 98%

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The impact of comorbid depression–diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment

Johnson

Zhang

Large

et al. 2019

Int. Psychogeriatr.

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Background:Mexican Americans suffer from a disproportionate burden of modifiable risk factors, which may contribute to the health disparities in mild cognitive impairment (MCI) and Alzheimer’s disease (AD).Objective:The purpose of this study was to elucidate the impact of comorbid depression and diabetes on proteomic outcomes among community-dwelling Mexican American adults and elders.Methods:Data from participants enrolled in the Health and Aging Brain among Latino Elders study was utilized. Participants were 50 or older and identified as Mexican American (N = 514). Cognition was assessed via neuropsychological test battery and diagnoses of MCI and AD adjudicated by consensus review. The sample was stratified into four groups: Depression only, Neither depression nor diabetes, Diabetes only, and Comorbid depression and diabetes. Proteomic profiles were created via support vector machine analyses.Results:In Mexican Americans, the proteomic profile of MCI may change based upon the presence of diabetes. The profile has a strong inflammatory component and diabetes increases metabolic markers in the profile.Conclusion:Medical comorbidities may impact the proteomics of MCI and AD, which lend support for a precision medicine approach to treating this disease.

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Section: Resultssupporting

confidence: 87%

Section: Blood Collection and Biomarker Analysismentioning

confidence: 98%

The impact of comorbid depression–diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment

Johnson

Zhang

Large

et al. 2019

Int. Psychogeriatr.

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“…In our prior work, we have generated and cross-validated an AD proteomic profile across platforms [28] , [31] , cohorts [28] , [30] , [32] , [41] , [42] , species (human, mouse) [31] , tissue (brain, serum, plasma) [31] , and ethnicities (non-Hispanic white, Mexican American) [28] , [43] . In our preliminary work, we found that this same proteomic profile could discriminate PD from AD [31] .…”

Section: Methodsmentioning

confidence: 99%

Potential two‐step proteomic signature for Parkinson's disease: Pilot analysis in the Harvard Biomarkers Study

O’Bryant

Edwards

Zhang

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction We sought to determine if our previously validated proteomic profile for detecting Alzheimer's disease would detect Parkinson's disease (PD) and distinguish PD from other neurodegenerative diseases. Methods Plasma samples were assayed from 150 patients of the Harvard Biomarkers Study (PD, n = 50; other neurodegenerative diseases, n = 50; healthy controls, n = 50) using electrochemiluminescence and Simoa platforms. Results The first step proteomic profile distinguished neurodegenerative diseases from controls with a diagnostic accuracy of 0.94. The second step profile distinguished PD cases from other neurodegenerative diseases with a diagnostic accuracy of 0.98. The proteomic profile differed in step 1 versus step 2, suggesting that a multistep proteomic profile algorithm to detecting and distinguishing between neurodegenerative diseases may be optimal. Discussion These data provide evidence of the potential use of a multitiered blood-based proteomic screening method for detecting individuals with neurodegenerative disease and then distinguishing PD from other neurodegenerative diseases.

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“…A meta-analysis of studies of cytokine levels in MCI failed to show an increase in inflammatory cytokines (IL-1β, IL-3, IL-6, IL-8, IL-10, IL-12, TNF-α and CRP) compared to healthy controls even though significant heterogeneity was observed between the studies (Saleem et al, 2015). However, a study of the proteomic profile in the amnestic subtype of MCI (aMCI) showed an increased expression of IL-10 in aMCI cases compared to normal controls in Mexican Americans (Edwards et al, 2015). IL10 gene variants rs1800896 and rs3024498, which were associated with incident MCR, have not, to our knowledge, been reported to predict incident MCI.…”

Section: Discussionmentioning

confidence: 99%

Association of anti-inflammatory cytokine IL10 polymorphisms with motoric cognitive risk syndrome in an Ashkenazi Jewish population

Sathyan

Barzilai

Atzmon

et al. 2017

Neurobiology of Aging

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Motoric cognitive risk (MCR) syndrome is a newly described pre-dementia syndrome characterized by the presence of cognitive complaints and slow gait, which is associated with increased risk of conversion to dementia. The underlying biological mechanisms for MCR have not yet been established. Neuroinflammation mediated through cytokines plays a pivotal role in the pathogenesis of dementia. Hence, our objective was to prospectively examine whether variations in cytokine genes (CRP, IFNG, IL1A, IL1B, IL4, IL6, IL10, IL18, TNF and IL12A) play a role in MCR incidence in 530 community-dwelling Ashkenazi Jewish adults age 65 and older without MCR or dementia at baseline enrolled in the LonGenity study. Over a median follow-up of 2.99 years, 70 participants developed MCR. Single nucleotide polymorphisms (SNPs) in the transcriptional regulatory regions of cytokine IL10, rs1800896 (Hazard ratio adjusted for age, gender and education (aHR) 1.667; 95% CI 1.198–2.321) and rs3024498 (aHR 1.926; 95% CI 1.315–2.822), were associated with incident MCR. Functional analysis using in-silico approaches indicated associated SNP rs3024498 'C' allele being the local expression quantitative trait locus (eQTL). Associated alleles of both the SNPs, rs1800896 and rs3024498 were implicated with over expression of IL10 gene. None of the variants in the neuroinflammatory pathway studied were associated with incident mild cognitive impairment syndrome. These observations support a role for the IL10 gene in dementia pathogenesis by increasing risk of developing MCR in older adults.

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Molecular Markers of Amnestic Mild Cognitive Impairment among Mexican Americans

Cited by 16 publications

References 43 publications

The impact of comorbid depression–diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment

The impact of comorbid depression–diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment

Potential two‐step proteomic signature for Parkinson's disease: Pilot analysis in the Harvard Biomarkers Study

Association of anti-inflammatory cytokine IL10 polymorphisms with motoric cognitive risk syndrome in an Ashkenazi Jewish population

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