| 1. |
- Bixby, H., et al.
(author)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Journal article (peer-reviewed)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 2. |
- Lind, Lars, et al.
(author)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
-
Journal article (peer-reviewed)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 3. |
- Carlsson, C.A., et al.
(author)
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An instrument for measuring ambient dose equivalent, H*(10)
- 1996
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In: Radiation Protection Dosimetry. - 0144-8420 .- 1742-3406. ; 67:1, s. 33-39
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Journal article (peer-reviewed)abstract
- The design and calibration of a small and simple instrument for measuring the ambient dose equivalent, H*(10), in photon fields is described. Comprising a thermoluminescence LiF dosemeter inside a 20 mm diameter PMMA sphere, it is capable of measuring the ambient dose equivalent with a nearly isotropic response. In the interval 0.1-100 mSv and for the energy range 30 keV to 1.25 MeV the energy response is within -31% and +15% relative to that of 137Cs gamma radiation (662 keV). In practical use, it is therefore sufficient to calibrate the instrument in a 137Cs gamma field using the corresponding conversion coefficient H*(10)/Kair taken from tabulations. The possibility of using the instrument to monitor the ambient dose equivalent for energies above 1.25 MeV is discussed and indicates that the range of applicability can be extended to 4.4 MeV with an energy response within -10% relative to 662 keV.
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| 4. |
- Sandborg, Michael, 1961-, et al.
(author)
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Shaping X-ray spectra with filters in X-ray diagnostics
- 1994
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In: Medical and Biological Engineering and Computing. - 0140-0118 .- 1741-0444. ; 32:4, s. 384-390
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Journal article (peer-reviewed)abstract
- The influence on image contrast, tube load and patient mean absorbed dose of different ways of shaping diagnostic X-ray spectra by placing filters in the beam is derived for two radiographic models (abdominal screen-film radiography and intra-oral, dental radiography) using a computational model. The filters are compared at either equal tube load (keeping tube potential constant) or equal contrast (adjusting the tube potential with the different filters), but always at equal energy imparted per unit area to the image receptor. Compared at equal tube load and relative to standard aluminium filtration, reductions in the mean absorbed dose in the patient of 15–25% can be achieved using filters of Cu, Ti, W and Au (increasing the tube load by 30–40% compared with standard aluminium filtration). However, contrast is also reduced by 7%. Compared at equal contrast, the dose reductions are smaller, about 10%. Filters of copper are generally recommended, as are filters of aluminium. The use of bandpass filters (K-edge filters) should be restricted to examinations where the need for substantial variation in tube potential from patient to patient is small. The benefit of using thicker filters than those commonly used today (increasing tube load by factors of 1.4–2.0 compared with no added filter) is small as the dose reduction is most rapid for small initial values of added filters, and the increase in tube load increases steadily with increasing filter thickness.
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| 5. |
- Barrios, C. A., et al.
(author)
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GaAs/AlGaAs buried-heterostructure vertical-cavity surface-emitting laser with semi-insulating GalnP : Fe regrowth
- 2000
-
In: Electronics Letters. - 0013-5194 .- 1350-911X. ; 36:18, s. 1542-1544
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Journal article (peer-reviewed)abstract
- The authors report the first results of a GaAs/AlGaAs buried-heterostructure vertical-cavity surface-emitting laser (VCSEL) with semi-insulating Ga0.51In0.49P:Fe (SI-GaInP:Fe) as the burying layer. Regrowth of SI-GaInP:Fe around 15 mu m diameter and 8 mu m tall VCSEL mesas was carried out by hydride vapour phase epitaxy (HVPE). Under room temperature continuous wave (CW) operation. the device exhibited a threshold current of 3.5mA, a differential quantum efficency of 33% and a light output power of 4.2mW. CW operation at temperatures up to 97 degrees C is also demonstrated.
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| 6. |
- Carlsson, Annelie, et al.
(author)
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Prevalence of IgA-antiendomysium and IgA-antigliadin autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children and adolescents
- 1999
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 103:6 I, s. 1248-1252
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Journal article (peer-reviewed)abstract
- Objective. This study was conducted to investigate the prevalence of celiac disease (CD) in children and adolescents at diagnosis of insulin- dependent diabetes mellitus (IDDM) before insulin treatment was started. Material and Methods. At diagnosis of IDDM, and before treatment was started, 115 children and adolescents were screened for IgA-antiendomysium (EMA) and IgA-antigliadin antibodies (AGA). Those found to be EMA-positive and/or AGA- positive were investigated further with intestinal biopsy. Results. Of the 115 patients, 2 had known CD at diagnosis of IDDM; of the remainder of patients, 6% (7/113) were found to be EMA-positive and 9% (10/113) were found to have AGA levels above normal. Of the 6 patients who underwent biopsy, 5 manifested villous atrophy. In addition, 2 patients with high EMA and AGA antibody titers refused biopsy, and 4 patients with low EMA and/or AGA titers were found to have normal titers at control before biopsy decision. Conclusion. Because the prevalence of CD at diagnosis of IDDM would seem to be 6% to 8%, screening for CD seems to be justified among patients with newly diagnosed IDDM.
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| 7. |
- Carlsson, C., et al.
(author)
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Performance characteristics of buried heterostructure VCSELs using semi-insulating GaInP : Fe regrowth
- 2001
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In: IEEE Journal of Quantum Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9197 .- 1558-1713. ; 37:7, s. 945-950
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Journal article (peer-reviewed)abstract
- We have fabricated GaAs-AlGaAs buried heterostructure vertical cavity surface emitting lasers, emitting at 850 nm, using semi-insulating GaInP:Fe regrowth and investigated their static properties. Lasers of different size (10-21 mum) have threshold currents in the range 2.8-7.0 mA, and produce a maximum output power of 1.7-6.0 mW at room temperature. The variation of threshold current with device size shows that the leakage current at the regrowth interface accounts for a significant part of the injection current. In spite of this, a differential quantum efficiency in the range 20%-30% is obtained which indicates that the regrowth interface is smooth and does not introduce any significant scattering loss. Studies of the transverse mode properties suggest that the GaInP provides weak guiding, resulting in single mode operation up to an output power of 0.7 mW and a beam divergence of only 6 degrees for lasers as large as 10 mum.
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| 8. |
- Delfani, P., et al.
(author)
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Deciphering systemic lupus erythematosus-associated serum biomarkers reflecting apoptosis and disease activity
- 2017
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In: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 26:4, s. 373-387
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of potential autoantigen(s); however, the lack of disease-specific protein signatures deciphering SLE and the underlying biological processes is striking and represents a key limitation. In this retrospective pilot study, we explored the immune system as a specific sensor for disease, in order to advance our understanding of SLE. To this end, we determined multiplexed serum protein expression profiles of crude SLE serum samples, using antibody microarrays. The aim was to identify differential immunoprofiles, or snapshots of the immune response modulated by the disease, reflecting apoptosis, a key process in the etiology of SLE and disease activity. The results showed that multiplexed panels of SLE-associated serum biomarkers could be decoded, in particular reflecting disease activity, but potentially the apoptosis process as well. While the former biomarkers could display a potential future use for prognosis, the latter biomarkers might help shed further light on the apoptosis process taking place in SLE.
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| 9. |
- Dong, R. C., et al.
(author)
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CSF metabolites associated with biomarkers of Alzheimer's disease pathology
- 2023
-
In: Frontiers in Aging Neuroscience. - 1663-4365. ; 15
-
Journal article (peer-reviewed)abstract
- IntroductionMetabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer's disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease.MethodsThe relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer's Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer's Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study.ResultsMetabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except A & beta;42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid & beta; (A & beta;40), & alpha;-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for A & beta;40 and & alpha;-synuclein.DiscussionThis study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.
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| 10. |
- Dong, R. C., et al.
(author)
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Identification of plasma metabolites associated with modifiable risk factors and endophenotypes reflecting Alzheimer's disease pathology
- 2023
-
In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284.
-
Journal article (peer-reviewed)abstract
- Modifiable factors can influence the risk for Alzheimer's disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and test their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms. The association between each of the 757 plasma metabolites and four modifiable factors was tested in the wisconsin registry for Alzheimer's prevention cohort of initially cognitively unimpaired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key pathophysiologies for AD, and four cognitive composite scores. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression. A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potential mediation effects include beta-cryptoxanthin in the association between MIND diet and preclinical Alzheimer cognitive composite score, hippurate between MIND diet and immediate learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and immediate learning. Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites can be employed as biomarkers for tracking these factors, and they provide a potential biological pathway of how modifiable factors influence the human body and AD risk.
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| 11. |
- Ennis, G. E., et al.
(author)
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Insulin resistance is related to cognitive decline but not change in CSF biomarkers of Alzheimer's disease in non-demented adults
- 2021
-
In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:1
-
Journal article (peer-reviewed)abstract
- Introduction We investigated whether insulin resistance (IR) was associated with longitudinal age-related change in cognition and biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration in middle-aged and older adults who were non-demented at baseline. Methods IR was measured with homeostatic model assessment of insulin resistance (HOMA2-IR). Core AD-related cerebrospinal fluid (CSF) biomarkers and cognition were assessed, respectively, on n = 212 (1 to 5 visits) and n = 1299 (1 to 6 visits). Linear mixed models tested whether HOMA2-IR moderated age-related change in CSF biomarkers and cognition. Linear regressions tested whether HOMA2-IR x apolipoprotein E epsilon 4 allele (APOE epsilon 4) carrier status predicted amyloid beta [A beta] chronicity (estimated duration of amyloid positron emission tomography [PET] positivity) (n = 253). Results Higher HOMA2-IR was associated with greater cognitive decline but not with changes in CSF biomarkers. HOMA2-IR x APOE4 was not related to A beta chronicity but was significantly associated with CSF phosphorylated tau (P-tau)(181)/A beta(42) level. Discussion In non-demented adults IR may not be directly associated with age-related change in AD biomarkers. Additional research is needed to determine mechanisms linking IR to cognitive decline.
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| 12. |
- Gallagher, R. L., et al.
(author)
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Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status
- 2023
-
In: Alzheimer's Research & Therapy. - 1758-9193. ; 15:1
-
Journal article (peer-reviewed)abstract
- BackgroundAlzheimer's disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited. Sensitive markers that may account for or predict cognitive dysfunction for individuals in early disease stages are critical.MethodsParticipants (n = 296) defined on A and T status and spanning the AD-clinical continuum underwent multi-shell diffusion-weighted magnetic resonance imaging to generate Neurite Orientation Dispersion and Density Imaging (NODDI) metrics, which were tested as markers of N. To better define N, we developed age- and sex-adjusted robust z-score values to quantify normal and AD-associated (abnormal) neurodegeneration in both cortical gray matter and subcortical white matter regions of interest. We used general logistic regression with receiver operating characteristic (ROC) and area under the curve (AUC) analysis to test whether NODDI metrics improved diagnostic accuracy compared to models that only relied on cerebrospinal fluid (CSF) A and T status (alone and in combination).ResultsUsing internal robust norms, we found that NODDI metrics correlate with worsening cognitive status and that NODDI captures early, AD neurodegenerative pathology in the gray matter of cognitively unimpaired, but A/T biomarker-positive, individuals. NODDI metrics utilized together with A and T status improved diagnostic prediction accuracy of AD clinical status, compared with models using CSF A and T status alone.ConclusionUsing a robust norms approach, we show that abnormal AD-related neurodegeneration can be detected among cognitively unimpaired individuals. Metrics derived from diffusion-weighted imaging are potential sensitive markers of N and could be considered for trial enrichment and as outcomes in clinical trials. However, given the small sample sizes, the exploratory nature of the work must be acknowledged.
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| 13. |
- Jonaitis, E. M., et al.
(author)
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Crosswalk study on blood collection-tube types for Alzheimer's disease biomarkers
- 2022
-
In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:1
-
Journal article (peer-reviewed)abstract
- Introduction Blood-based Alzheimer's disease (AD) biomarkers show promise, but pre-analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [A beta]42${\rm{A\beta }}]{_{42}}$, A beta 40${\rm{A}}{{{\beta}}_{40}}$, phosphorylatedtau[p-tau181${\rm{phosphorylated\;tau\;[p - ta}}{{\rm{u}}_{181}}$, total tau [t-tau], neurofilament light chain [NfL], A beta 4240,${\rm{A}}{{{\beta}}_{\frac{{42}}{{40}}}},$ and p-tau181A beta 42$\frac{{{\rm{p - ta}}{{\rm{u}}_{181}}}}{{{\rm{A}}{{{\beta}}_{42}}}}$) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum). Methods Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography-positive and -negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention. We modeled AD biomarker values observed in EDTA plasma versus heparin plasma and serum, and assessed correspondence with brain amyloidosis. Results Results suggested bias due to tube type, but crosswalks are possible for some analytes, with excellent model fit for NfL (R2${{\rm{R}}<^>2}\;$= 0.94), adequate for amyloid (R2${{\rm{R}}<^>2}\;$= 0.40-0.69), and weaker for t-tau (R2${{\rm{R}}<^>2}\;$= 0.04-0.42) and p-tau181${\rm{p - ta}}{{\rm{u}}_{181}}$ ( R2${{\rm{R}}<^>2}\;$= 0.22-0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma pTau181A beta 42$\frac{{{\rm{pTa}}{{\rm{u}}_{181}}}}{{{\rm{A}}{\beta _{42}}}}$ (d$d\;$= 1.29). Discussion AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood.
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| 14. |
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| 15. |
- Lenngren, C. A., et al.
(author)
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Airfield pavement structural analyses and design in Sweden
- 2002
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In: Bearing Capacity Of Roads Railways and Airfields. - London : CRC Press. - 9781000108101 - 9789058093967 ; , s. 325-334
-
Book chapter (other academic/artistic)abstract
- The present paper discusses how a mechanistic design process evolved for airfields in Sweden and how it is being used. Also, a sensitivity study is presented showing parameter influence on the bearing capacity expressed in Pavement Classification Number (PCN). For example, how do revised asphalt strain criteria affect the resulting PCN-value? Other parameters included the stiffness of the asphalt layer, the base layer, and subgrade during the spring thaw period. An equivalent number of standard wheel load (ESWL) was calculated for some commonly used aircrafts on selected Swedish airfield pavements. These calculations were based on the tensile strain at bottom of the asphalt layer. Thus, the Aircraft Classification Number (ACN) derived in this manner could be compared to the existing status. The paper also discusses some future applications using high-speed rolling deflectometers.
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| 16. |
- Ma, Y., et al.
(author)
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Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values
- 2021
-
In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
-
Journal article (peer-reviewed)abstract
- Introduction Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland-Altman plot, paired t test, Pitman-Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R-2 except for converting P-tau between batches 1 and 3. Discussion Between-batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.
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| 17. |
- Mcelhinney, L. M., et al.
(author)
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High prevalence of Seoul hantavirus in a breeding colony of pet rats
- 2017
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In: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 145:15, s. 3115-3124
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Journal article (peer-reviewed)abstract
- As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.
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| 18. |
- Morrow, A., et al.
(author)
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Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation
- 2022
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 90:2, s. 667-680
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Journal article (peer-reviewed)abstract
- Background: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available. Objective: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation. Methods: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models. Results: No SMs were significantly associated with AD diagnosis, mild cognitive impairment, or amyloid biomarkers. Phosphorylated tau, neurofilament light, alpha-synuclein, neurogranin, soluble triggering receptor expressed on myeloid cells 2, and chitinase-3-like-protein 1 were each significantly, positively associated with at least 5 of the SMs. Conclusion: The associations between SMs and biomarkers of neurodegeneration and neuroinflammation, but not biomarkers of amyloid or diagnosis of AD, point to SMs as potential biomarkers for neurodegeneration and neuroinflammation that may not be AD-specific.
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| 19. |
- Ohlin, M., et al.
(author)
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Epstein-Barr virus-induced transformation of human B lymphocytes : the effect of l-leucyl-l-leucine methyl ester on inhibitory T cell populations
- 1992
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In: Immunology Letters. - 0165-2478. ; 34:3, s. 221-228
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Journal article (peer-reviewed)abstract
- Epstein-Barr virus-mediated transformation of human B lymphocytes is inhibited by human T lymphocytes as well as by interferon-γ. Removal of the inhibitory cell populations is essential in order to achieve successful transformation in vitro. Cells with the capacity to inhibit outgrowth of lymphoblastoid cell lines can be removed by pretreatment of peripheral blood mononuclear cells with l-leucyl-l-leucine methyl ester. This treatment eliminates monocytes, NK-cells and a CD8+ T cell subpopulation. We now show that such treatment also has toxic effects on other human T cell populations. In addition, CD4+ and/or CD8+ lymphocytes are demonstrated to contain effector cell activities which inhibit outgrowth of EBV-transformed B cells. This inhibitory activity is abolished after treatment of peripheral blood mononuclear cells or purified CD4+ T cells with l-leucyl-l-leucine methyl ester. No evidence was found for a selective toxicity against any subset within the CD4+ or CD8+ T cell populations. However, the capacity of the treated cells, both peripheral blood mononuclear cells and purified CD4+ T lymphocytes, to produce mRNA encoding IFN-γ, a protein previously shown to downregulate outgrowth of EBV-transformed B cells, was selectively impaired. The results obtained suggest a role for CD4+ T cells to inhibit EBV-induced transformation of B cells.
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| 20. |
- Panyard, D. J., et al.
(author)
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Large-scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease
- 2023
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In: Alzheimers & Dementia. - 1552-5260.
-
Journal article (peer-reviewed)abstract
- INTRODUCTIONA hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest. METHODSWe conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation. RESULTSWe identified 61 proteins significantly associated with the AT category (P < 5.46 x 10(-5)) and 636 significant protein-biomarker associations (P < 6.07 x 10(-6)). Proteins from glucose and carbon metabolism pathways were enriched among amyloid- and tau-associated proteins, including malate dehydrogenase and aldolase A, whose associations with tau were replicated in an independent cohort (n = 717). CSF metabolomics identified and replicated an association of succinylcarnitine with phosphorylated tau and other biomarkers. DISCUSSIONThese results implicate glucose and carbon metabolic dysregulation and increased CSF succinylcarnitine levels with amyloid and tau pathology in AD. HIGHLIGHTSCerebrospinal fluid (CSF) proteome enriched for extracellular, neuronal, immune, and protein processing.Glucose/carbon metabolic pathways enriched among amyloid/tau-associated proteins.Key glucose/carbon metabolism protein associations independently replicated.CSF proteome outperformed other omics data in predicting amyloid/tau positivity.CSF metabolomics identified and replicated a succinylcarnitine-phosphorylated tau association.
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| 21. |
- Panyard, D. J., et al.
(author)
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Liver-Specific Polygenic Risk Score Is Associated with Alzheimer's Disease Diagnosis
- 2023
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 92:2, s. 395-409
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Journal article (peer-reviewed)abstract
- Background: Our understanding of the pathophysiology underlying Alzheimer's disease (AD) has benefited from genomic analyses, including those that leverage polygenic risk score (PRS) models of disease. The use of functional annotation has been able to improve the power of genomic models. Objective: We sought to leverage genomic functional annotations to build tissue-specific AD PRS models and study their relationship with AD and its biomarkers. Methods: We built 13 tissue-specific AD PRS and studied the scores' relationships with AD diagnosis, cerebrospinal fluid (CSF) amyloid, CSF tau, and other CSF biomarkers in two longitudinal cohort studies of AD. Results: The AD PRS model that was most predictive of AD diagnosis (even without APOE) was the liver AD PRS: n = 1,115; odds ratio = 2.15 (1.67-2.78), p = 3.62x10(-9). The liver AD PRS was also statistically significantly associated with cerebrospinal fluid biomarker evidence of amyloid-beta (A beta(42):A beta(40) ratio, p = 3.53x10(-6)) and the phosphorylated tau:amyloid beta ratio (p = 1.45x10(-5)). Conclusion: These findings provide further evidence of the role of the liver-functional genome in AD and the benefits of incorporating functional annotation into genomic research.
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| 22. |
- Pellettieri, L, et al.
(author)
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Serum immunocomplexes in patients with subarachnoid hemorrhage.
- 1986
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In: Neurosurgery. - 0148-396X .- 1524-4040. ; 19:5, s. 767-771
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Journal article (peer-reviewed)abstract
- Immunocomplexes (IC) in serum were analyzed in 54 patients with subarachnoid hemorrhage (SAH) from ruptured arterial aneurysms. A previous study had shown that patients with SAH and vasospasm had a significantly higher incidence of ICs in the blood than patients without vasospasm. The aim of the present study was to study how the IC content varied with time and compare this pattern with the clinical picture. Forty-two patients presented clinical or radiological signs of cerebral vasospasm during their hospital stays, whereas 12 patients showed no such signs. The patients with vasospasm had a significantly higher amount of ICs in serum than those without vasospasm. In 37 patients with vasospasm, the changes of IC content during the 1st weeks after SAH correlated well with the clinical course. Data indicated that a high IC content preceded the onset of vasospasm and a low content preceded clinical improvement. This observation supports the idea that the presence of ICs might be the cause and not the result of vasospasm.
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| 23. |
- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 24. |
- Vogt, N. M., et al.
(author)
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Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults
- 2022
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 65-76
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Journal article (peer-reviewed)abstract
- Introduction: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42/Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. Results: We observed a significant CSF Aβ42/Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment. © 2021 the Alzheimer's Association
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