A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

Bawa, Kritleen K.; Krance, Saffire H.; Herrmann, Nathan; Cogo-Moreira, Hugo; Ouk, Michael; Yu, Di; Wu, Che‐Yuan; Black, Sandra E.; Lanctôt, Krista L.; Swardfager, Walter

doi:10.1186/s12974-020-01750-3

Cited by 39 publications

(26 citation statements)

References 62 publications

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“…In Alzheimer's disease patients, MPO peripheral blood concentration was significantly higher in these patients compared to control [ 139 ]. Furthermore, this biochemical measurement is considered reflective of neutrophil activity in this disease [ 140 ]. (See “Secondary sites of MPO localization” section above for more details on MPO and Alzheimer's disease).…”

Section: Mpo Usefulness As a Biomarker In Disease Statesmentioning

confidence: 99%

The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery

Siraki

2021

Redox Biology

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This review provides a practical guide to myeloperoxidase (MPO) and presents to the reader the diversity of its presence in biology. The review provides a historical background, from peroxidase activity to the discovery of MPO, to its role in disease and drug development. MPO is discussed in terms of its necessity, as specific individuals lack MPO expression. An underlying theme presented throughout brings up the question of the benefit and burden of MPO activity. Enzyme structure is discussed, including accurate masses and glycosylation sites. The catalytic cycle of MPO and its corresponding pathways are presented, with a discussion of the importance of the redox couples of the different states of MPO. Cell lines expressing MPO are discussed and practically summarized for the reader, and locations of MPO (primary and secondary) are provided. Useful methods of MPO detection are discussed, and how these can be used for studying disease processes are implied through the presentation of MPO as a biomarker. The presence of MPO in neutrophil extracellular traps is presented, and the activators of the former are provided. Lastly, the transition from drug metabolism to a target for drug development is where the review concludes.

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Section: Mpo Usefulness As a Biomarker In Disease Statesmentioning

confidence: 99%

The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery

Siraki

2021

Redox Biology

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“…Different models are available to disentangle trait features and methodological features, (Eid et al, 2003;Eid et al, 2008) which might be extended into longitudinal designs for this purpose (Geiser et al, 2010). We and others have found reliable aggregate estimates via CFA for different types of measures in AD (e.g., inflammatory/immunological; Swardfager et al, 2017;Bawa et al, 2020), but the behavior of these measures over time has not been evaluated. The principles and methods applied here might also be considered in the development of composite surrogate trial outcome measures, to gain some insight into how repeated measures using those instruments would track change prior to their use in trials.…”

Section: Discussionmentioning

confidence: 92%

Questioning the Meaning of a Change on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog): Noncomparable Scores and Item-Specific Effects Over Time

et al. 2020

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Longitudinal invariance indicates that a construct is measured over time in the same way, and this fundamental scale property is a sine qua non to track change over time using ordinary mean comparisons. The Alzheimer’s Disease Assessment Scale–cognitive (ADAS-Cog) and its subscale scores are often used to monitor the progression of Alzheimer’s disease, but longitudinal invariance has not been formally evaluated. A configural invariance model was used to evaluate ADAS-Cog data as a three correlated factors structure for two visits over 6 months, and four visits over 2 years (baseline, 6, 12, and 24 months) among 341 participants with Alzheimer’s disease. We also attempted to model ADAS-Cog subscales individually, and furthermore added item-specific latent variables. Neither the three-correlated factors ADAS-Cog model, nor its subscales viewed unidimensionally, achieved longitudinal configural invariance under a traditional modeling approach. No subscale achieved scalar invariance when considered unidimensional across 6 months or 2 years of assessment. In models accounting for item-specific effects, configural and metric invariance were achieved for language and memory subscales. Although some of the ADAS-Cog individual items were reliable, comparisons of summed ADAS-Cog scores and subscale scores over time may not be meaningful due to a lack of longitudinal invariance.

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“…On the other hand, LCN2 deficiency in an AD mouse model led to decreased iron accumulation in the hippocampus but not to altered symptoms, amyloid plaque load, or glial activation [ 46 ]. Interestingly, peripheral LCN2 was shown to be associated with executive dysfunction in preclinical and mild AD patients rather than with memory impairment [ 20 , 47 ], which is the typical early symptom of AD-related pathology. This suggests that LCN2 might possibly reflect secondary mechanisms in the complex pathophysiology of AD.…”

Section: Discussionmentioning

confidence: 99%

Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers

et al. 2022

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Background Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer’s disease (p = 0.013). Conclusions Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.

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A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease

Cited by 39 publications

References 62 publications

The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery

The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery

Questioning the Meaning of a Change on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog): Noncomparable Scores and Item-Specific Effects Over Time

Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers

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