Serum proteins mediate depression’s association with dementia

Royall, Donald R.; Al-Rubaye, Safa; Bishnoi, Ram J.; Palmer, Raymond F.

doi:10.1371/journal.pone.0175790

Cited by 22 publications

(19 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…INFLAMMATION accounts for 5%–10% of dT2A's variance, which we have previously shown to be strongly associated with CDR‐SB and the diagnosis of clinical “AD” [16]. Its effect on δ is independent of other recognized dementia risks (e.g., age, APOE, and depression) which are mediated by yet other serum proteins [11–13]. In their aggregate, INFLAMMATION and those dementia risks account for between 24% (ADNI) to 38% (TARCC) of dT2A's variance.…”

Section: Discussionmentioning

confidence: 99%

“…Unmodeled influences on the observed protein concentrations could explain nondementing effects of the same biomarker in other organs or even in brain, given that not all cognitive domains are functionally salient [3,45]. Several δ‐related serum protein biomarkers mediate both age and depression's independent and mutually adjusted effects on δ (apparently as contributors to independent competing processes) [11,13].…”

Section: Discussionmentioning

confidence: 99%

“…Many of these associations appear to have profound ethnicity effects in the TARCC [9,10]. We have also published the serum protein mediators of δ's specific associations with several well‐recognized dementia risks (including age, depressive symptoms, and the apolipoprotein [APOE] ε4 allele) [11–13]. These associations have been confirmed in random subsets of the TARCC's large sample.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Bishnoi

Pavlik

Massman

et al. 2019

Alz & Dem Diag Ass & Dis Mo

Self Cite

View full text Add to dashboard Cite

Introduction Dementia severity can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ's blood‐based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we recently engineered a δ homolog from observed cognitive performance measures common to both projects (i.e., “dT2A”). Methods We used nine rationally chosen peripheral blood‐based protein biomarkers as indicators of a latent variable “INFLAMMATION”. We then associated that construct with dT2A in structural equation models adjusted for age, gender, depressive symptoms, and apolipoprotein E (APOE) ε4 allelic burden. Significant factor loadings and INFLAMMATION's association with dT2A were confirmed in random splits of TARCC's relatively large sample, and across biofluids in the ADNI. Results Nine proteins measured in serum (TARCC) or plasma (ADNI) explained ≅10% of dT2A's variance in both samples, independently of age, APOE, education, and gender. All loaded significantly on INFLAMMATION, and positively or negatively, depending on their known roles are PRO‐ or ANTI‐inflammatory proteins, respectively. The parameters of interest were confirmed across random 50% splits of the TARCC's sample, and replicated across biofluids in the ADNI. Discussion These results suggest that SEM can be used to replicate biomarker findings across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood‐based protein levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Bishnoi

Pavlik

Massman

et al. 2019

Alz & Dem Diag Ass & Dis Mo

Self Cite

View full text Add to dashboard Cite

show abstract

“…All six selected proteins have been previously reported to associate with dementia phenotype “δ” in ethnicity-adjusted models from TARCC cohort 41,42 . Details about concept and utility of δ is can be obtained from past publications 43–45 46 .…”

Section: Mainmentioning

confidence: 99%

Serum proteins can successfully predict self-reported ethnicity: Implications for precision-medicine

Bishnoi

Palmer

Royall

2017

Preprint

View full text Add to dashboard Cite

The effects of inter-individual variability on disease treatment and prevention are important to the goals of “precision medicine” 1. In biomedical research, consideration of racial or ethnic differences allows generation and exploration of hypotheses about interactions among genetic and environmental factors responsible for differential medical outcomes. The US National Institutes of Health, therefore recommends adequate participation of subjects from ethnic minority groups in research studies. Nevertheless, considerable debate has focused on validity of race or ethnicity as biological construct 2. Inconsistent definition of race/ethnicity and insignificant genetic variations between ethnic groups have invited disregard to this construct 3. On the contrary, differences in prevalence, expression and outcomes of various diseases among ethnic groups argue for continued and focused attention to ethnicity as important predicting variable. In context of Alzheimer’s disease (AD), we have previously reported that ethnicity does moderates the proteomic markers of dementia 4. Here, we attempted to classify and predict selfreported ethnicity (Hispanic or non-Hispanic white, [NHW]) using a limited serum profile of 107 proteins. Random Forest (RF) classification method was able to discriminate those two ethnicities with 95% accuracy and could successfully predict ethnicity in an independent test-set (Area under ROC curve: 0.97). Variable selection method led to a condensed set of six proteins which yielded comparable classification and prediction accuracy. Our results provide preliminary evidence for proteomic variability between ethnic groups, and biological validity of ethnicity construct. Moreover, they also offer an opportunity to exploit these differences towards the objectives of precision medicine.

show abstract

“…Contemporary data emphasize the role of processes of neuroplasticity and neuroinflammation in pathogenesis of endogenous mental disorders, including schizophrenia [30][31][32][33]. In particular, it has been shown that high activity of leukocyte elastase (LE) and alpha-1 proteinase inhibitor (α − 1 − PI) has been associated with exacerbation of endogenous mental disorders, while in remission their activity decreased [33,34]. Moreover, these immunological parameters not only reflected the acuity of illness, but also may precede the clinical signs of relapse [33].…”

Section: Introductionmentioning

confidence: 99%

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients

2018

J. Integr. Neurosci.

View full text Add to dashboard Cite

The aim of this study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic subjects. Correlation and regression analyses of quantitative Positive And Negative Syndromes Scale clinical scores, together with background electroencephalographic spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed for 50 female subjects with hallucinatory-delusional disorders such as attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of a syndrome based treatment course were matched with Positive And Negative Syndromes Scale clinical scores of the same subjects after a treatment course to the stage of establishment of remission. The multiple linear regression equations were created which were described by only three or four (from an initial 80) background electroencephalographic parameters and one of four immunological parameters. These mathematical models allowed prediction of 65-76% of Positive and Negative Syndromes Scale score variance after a treatment course. The data obtained may be useful for elaboration of methods for individual quantitative prediction of treatment outcome for schizophrenic subjects.

show abstract

Serum proteins mediate depression’s association with dementia

Cited by 22 publications

References 59 publications

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Serum proteins can successfully predict self-reported ethnicity: Implications for precision-medicine

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients

Contact Info

Product

Resources

About