Cognitive ability in Down syndrome and its relationship to urinary neopterin, a marker of activated cellular immunity

Zis, Panagiotis; Strydom, André; Buckley, David; Adekitan, Daniel; McHugh, Patrick

doi:10.1016/j.neulet.2016.11.023

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…The results of this study clearly confirm previous reports that significantly higher levels of hs-CRP and neopterin were observed in T2D complicated with foot ulcers [19,21]. Higher serum levels of neopterin among T2D compared with T1D patients indicates activation of cell-mediated immune response and increase in reactive oxygen species [22,23]. Previous studies showed that neopterin levels were influenced by proinflammatory and anti-inflammatory cytokines and this explains the insignificant correlation between serum neopterin and hs-CRP levels observed in this study [24].…”

Section: Discussionsupporting

confidence: 90%

Assessment of serum neopterin as an inflammatory and cardiovascular marker in type 1 and 2 diabetes complicated by diabetic foot syndrome: a comparative study

Al-Nimer¹,

Dezayee

2018

Clinical Diabetology

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Introduction. Neopterin is a byproduct of nerve transmitter coenzyme that is synthesized and released by macrophages and T-lymphocytes. It is a useful inflammatory marker of diabetes progression, as its levels increase with the progression of the disease from prediabetes to type 2 diabetes (T2D). This study aimed to compare serum neopterin levels between type-1 and type-2 diabetes patients with diabetic foot syndrome (DFS), and assess the relation between serum neopterin levels and cardiometabolic risk factors. Materials and methods. This observational cross-sectional study was carried out in the Centre of Diabetes Mellitus in Erbil, Iraq from 1 st January to 31 st December 2016. A total of 30 healthy subjects and 140 patients with DFS [70 patients with type 1 diabetes (T1D) and 70 patients with T2D] were enrolled in the study. The main outcome measurements included anthropometric measurements, blood pressure, fasting serum glucose, glycated haemoglobin, lipid profile, neopterin and high sensitivity C-reactive protein (hs-CRP). Results. Serum neopterin levels of T2D patients were significantly (p < 0.001) higher than the corresponding levels of T1D patients (18.6 ± 2.1 nmol/L vs. 12.6 ± 1.3 nmol/L). The changes in the serum neopterin levels were related to cardiometabolic risk factors. In T1D, a significant positive correlation between serum levels of neopterin and diastolic blood pressure were observed, while in T2D the significant positive correlation was found between fasting serum triglyceride levels and neopterin levels. Serum levels of neopterin were insignificantly correlated with hs-CRP in T1D and T2D. Conclusions. In patients with DFS, serum neopterin levels are significantly higher in those with T2D compared with T1D patients. Neopterin levels are not related to the grading of DFS, but are invariably related to cardiometabolic risk factors.

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Section: Discussionsupporting

confidence: 90%

Assessment of serum neopterin as an inflammatory and cardiovascular marker in type 1 and 2 diabetes complicated by diabetic foot syndrome: a comparative study

Al-Nimer¹,

Dezayee

2018

Clinical Diabetology

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“…Numerous reports have described a relationship between the presence of AD in Down syndrome (DS) and the generation of epileptic seizures [ 31 , 182 , 183 , 184 , 185 , 186 , 187 , 188 ], correlating with a progressive deterioration of cognitive and motor functions. Both conditions appear in older patients with DS and up to 84% demented patients with DS develop seizures [ 8 ].…”

Section: Seizures In Ftdp-17 and Other Dementiasmentioning

confidence: 99%

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Sánchez

García-Cabrero

Sánchez-Elexpuru

et al. 2018

IJMS

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Patients with dementia present epilepsy more frequently than the general population. Seizures are more common in patients with Alzheimer’s disease (AD), dementia with Lewy bodies (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) than in other dementias. Missense mutations in the microtubule associated protein tau (MAPT) gene have been found to cause familial FTD and PSP, while the P301S mutation in MAPT has been associated with early-onset fast progressive dementia and the presence of seizures. Brains of patients with AD, LBD, FTD and PSP show hyperphosphorylated tau aggregates, amyloid-β plaques and neuropil threads. Increasing evidence suggests the existence of overlapping mechanisms related to the generation of network hyperexcitability and cognitive decline. Neuronal overexpression of tau with various mutations found in FTD with parkinsonism-linked to chromosome 17 (FTDP-17) in mice produces epileptic activity. On the other hand, the use of certain antiepileptic drugs in animal models with AD prevents cognitive impairment. Further efforts should be made to search for plausible common targets for both conditions. Moreover, attempts should also be made to evaluate the use of drugs targeting tau and amyloid-β as suitable pharmacological interventions in epileptic disorders. The diagnosis of dementia and epilepsy in early stages of those diseases may be helpful for the initiation of treatments that could prevent the generation of epileptic activity and cognitive deterioration.

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“…Similarly to the findings in plasma neopterin levels described above, urine neopterin might also have a potential as a biomarker of AD in DS. In a longitudinal study involving individuals with DS it was shown that neopterin/creatinine levels correlated with cognitive performance over time [87].…”

Section: Fluid Biomarkers Of Ad In Ds (Table 2)mentioning

confidence: 99%

Clinical aspects and biomarkers of Alzheimer's disease in Down syndrome

Zis

Strydom

2018

Free Radical Biology and Medicine

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Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication. We suggest that the clinical presentation in DS (prominent memory decline and behavioral symptoms, and early development of myoclonus and seizures) are similar to the clinical features associated with APP mutations that is known to have an increased Aβ42/ Aβ40 ratio, and highlight the relative lack of vascular complications associated with cerebral amyloid angiopathy in DS in comparison with those rare individuals with FAD due to duplication APP. We consider the biomarker evidence associated with DS and DSd with reference to Aβ peptide levels and oxidative stress, and suggest future directions for research to explore the potential mechanisms associated with the clinical presentation of DSd.

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Cognitive ability in Down syndrome and its relationship to urinary neopterin, a marker of activated cellular immunity

Abstract: Urine neopterin may have potential as a biomarker for memory decline in Down syndrome, and could potentially also help to track progression of mild cognitive impairment (MCI) to Alzheimer's disease in other high risk populations.

Cited by 13 publications

References 34 publications

Assessment of serum neopterin as an inflammatory and cardiovascular marker in type 1 and 2 diabetes complicated by diabetic foot syndrome: a comparative study

Assessment of serum neopterin as an inflammatory and cardiovascular marker in type 1 and 2 diabetes complicated by diabetic foot syndrome: a comparative study

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Clinical aspects and biomarkers of Alzheimer's disease in Down syndrome

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