Probing the proteome to explore potential correlates of increased Alzheimer's-related cerebrovascular disease in adults with Down syndrome.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination.

Alzheimer-Related Cerebrovascular Disease in Down Syndrome.

OBJECTIVE: Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status. METHODS: Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status. RESULTS: There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct. INTERPRETATION: The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165-1177.

Corrigendum to "Enrichment, sources, and distributions of toxic elements in the farming land's topsoil near a heavily industrialized area of central Bangladesh, and associated risks assessment" [Heliyon 9 (4) 2023 e15078].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15078.].

Enrichment, sources, and distributions of toxic elements in the farming land's topsoil near a heavily industrialized area of central Bangladesh, and associated risks assessment.

Toxic element accumulation in the surrounding soils of the advanced industry- and agriculture-oriented areas may lead to severe environmental degradation and harmful impact on inhabitants. This work examined the concentration of some concerned toxic elements (Cr, Pb, Cd, Cu, As, and Ni) in the representative topsoil from 10 industrially contaminated sites in central Bangladesh (Narayanganj district) using an Inductively Coupled Plasma Mass Spectrometer concerning the probable ecological and human health risks. The mean concentrations (mg/kg) of the elements were found in the order of Ni (58.1 ± 11.8) > Pb (34.1 ± 14.3) > Cr (32.1 ± 6.77) > Cu (14.5 ± 3.30) > Cd (2.74 ± 1.08) > As (1.49 ± 0.43). The findings pointed out that diversified manmade events enhanced the intensities of elemental contamination through the studied sites. Source analysis showed that Cr, Pb, As, and Cd may originate from industrial wastewater and agricultural activities, whereas Cu and Ni came from natural sources. The geo-accumulation index level for Cd (1.70-3.39) was determined as grade 3 (moderately to strongly polluted), the enrichment factor score for Cd (13.9) fell in the very severe enhanced category (cluster 5), and the highest contamination factor value was found for Cd (15.7). The contamination degree values for all the tested elements signify a moderate to severe contamination grade; conversely, pollution load index levels depicted the nonexistence of elemental pollution. The assessment revealed serious Cd pollution in agricultural soils and moderate to significant potential ecological risk for the rest of the examined toxic elements. Furthermore, hazard index values exceeded the safe exposure levels, indicating that there was potential non-carcinogenic risk in the soils for children and adults. Ingestion exposure had much higher carcinogenic risk values than inhalation and cutaneous exposure, and children are exposed to considerable carcinogenic hazards. Therefore, it is suggested that the harmful practices that expose this farming soil to contaminants should be stopped immediately and effective environment-friendly techniques of waste management and effluent treatment should be employed in the study area.

Obstructive sleep apnea, cerebrovascular disease, and amyloid in older adults with Down syndrome across the Alzheimer's continuum.

We determined the extent to which obstructive sleep apnea (OSA) is associated with increased cerebrovascular disease and amyloid burden, and the relation of the two processes across clinical Alzheimer's disease (AD) diagnostic groups in adults with Down syndrome (DS). Adults with DS from the Biomarkers of Alzheimer's Disease in Down Syndrome (ADDS) study were included given available research MRI (n = 116; 50 ± 8 years; 42% women) and amyloid PET scans (n = 71; 50 ± 7 years; 39% women) at the time of analysis. Participants were characterized as cognitively stable (CS; 64%), with mild cognitive impairment-DS (MCI-DS; 23%), with possible AD dementia (5%), or with definite AD dementia (8%). OSA was determined via medical records and interviews. Models tested the effect of OSA on MRI-derived cerebrovascular biomarkers and PET-derived amyloid burden, and the moderating effect of OSA and AD diagnosis on biomarkers. OSA was reported in 39% of participants, which did not differ by clinical AD diagnostic group. OSA was not associated with cerebrovascular biomarkers but was associated with greater cortical amyloid burden. White matter hyperintensity (WMH) volume (primarily in the parietal lobe), enlarged perivascular spaces, and cortical and striatal amyloid burden were greater across clinical AD diagnostic groups (CS