| 301. |
- Salvadó, Gemma, et al.
(författare)
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Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi-cohort study
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:7, s. 2943-2955
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases.Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of A beta 42, A beta 40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, alpha-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit).Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/A beta 42 alone (R-2 >= 0.31) or together with NfL (R-2 = 0.25), while p-tau/A beta 42 (R-2 >= 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/A beta 42 (AUC >= 0.87) and p-tau/A beta 42 together with NfL (AUC >= 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively.Discussion: P-tau/A beta 42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.
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| 302. |
- Salvado, G., et al.
(författare)
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The protective gene dose effect of the APOE epsilon 2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) epsilon 2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired epsilon 2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of epsilon 2 genotypic groups were compared to each other and to the reference group (APOE epsilon 3/epsilon 3). Results: Carrying at least one epsilon 2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE epsilon 2 homozygotes, but not APOE epsilon 2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-beta deposition, the larger GM volumes in key brain regions may confer APOE epsilon 2 homozygotes additional protection against AD-related cognitive decline.
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| 303. |
- Salvadó, Gemma, et al.
(författare)
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The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
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| 304. |
- Samuelsson, Jessica, et al.
(författare)
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Associations between dietary patterns and dementia-related neuroimaging markers
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:10, s. 4629-4640
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe exploration of associations between dietary patterns and dementia-related neuroimaging markers can provide insights on food combinations that may impact brain integrity. METHODSData were derived from the Swedish Gothenburg H70 Birth Cohort Study (n = 610). Three dietary patterns were obtained using principal component analysis. Magnetic resonance imaging markers included cortical thickness, an Alzheimer's disease (AD) signature score, small vessel disease, and white matter microstructural integrity. Adjusted linear/ordinal regression analyses were performed. RESULTSA high-protein and alcohol dietary pattern was negatively associated with cortical thickness in the whole brain (Beta: -0.011; 95% confidence interval [CI]: -0.018 to -0.003), and with an Alzheimer's disease cortical thickness signature score (Beta: -0.013; 95% CI: -0.024 to -0.001). A positive association was found between a Mediterranean-like dietary pattern and white matter microstructural integrity (Beta: 0.078; 95% CI: 0.002-0.154). No associations were found with a Western-like dietary pattern. DISCUSSIONDietary patterns may impact brain integrity through neurodegenerative and vascular pathways. HighlightsCertain dietary patterns were associated with dementia-related neuroimaging markers.A Mediterranean dietary pattern was positively associated with white matter microstructure.A high-protein and alcohol pattern was negatively associated with cortical thickness.
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| 305. |
- Samuelsson, Jessica, et al.
(författare)
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Associations of dietary patterns and CSF biomarkers for Alzheimer’s disease in a population-based sample of 70-year-olds
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279.
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Konferensbidrag (refereegranskat)abstract
- Background: Diet could be a modifiable factor in the prevention of Alzheimer’s disease (AD). Western-style dietary patterns are considered to increase the risk, while Mediterranean-style dietary patterns are considered protective. The aim of this study was to investigate the relation between dietary patterns and CSF biomarkers of relevance for AD. Method: Data was derived from the population based Gothenburg H70 Birth Cohort Studies in Gothenburg, Sweden (n=1203). CSF levels of β-amyloid (Aβ)42, total tau, and phosphorylated tau were measured with ELISA. Dietary intake was determined by the diet history method (n=861). Principal component analysis were performed to reduce 21 food groups into factors representing dietary patterns. Logistic regression analyses, with CSF biomarkers as dependent variables (pathological/not pathological), and linear regression analyses with CSF biomarkers as continuous variables, were performed on the dementia-free participants with both CSF and dietary data (n=269, 49% women). Analyses were adjusted for APOE ε4 status, energy intake, education, BMI, physical activity and sex. Analyses were also performed stratified by sex. Result: Four factors representing dietary patterns were derived from the principal component analysis. A western-style dietary pattern, a Mediterranean-style dietary pattern, a mixed dietary pattern with alcoholic beverages and a dietary pattern of high fat dairy products, eggs and refined cereal products. The odds ratio of having pathological values of total tau was higher among those with a higher compliance to a western-style dietary pattern (OR 1.37; 95%CI 1.02-1.80). The linear regression model indicate the same trend (r2=0.06, B=0.04, p=0.08). When stratified by sex, the odds ratio of having pathological values of phosphorylated tau was higher for those with a higher intake of high fat dairy products, eggs and refined cereal products among men (OR 3.38; 95%CI 1.22-9.36). We could not find an association between the other dietary patterns and CSF biomarkers. Conclusion: Our results indicate an association between western-style dietary patterns and increased levels of total tau and phosphorylated tau. However, there was no relation between a healthier Mediterranean-style dietary pattern and CSF biomarkers for AD.
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| 306. |
- Samuelsson, Jessica, et al.
(författare)
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Interactions between dietary patterns and genetic factors in relation to incident dementia among 70-year-olds
- 2021
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279.
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Konferensbidrag (refereegranskat)abstract
- Abstract Background Genetic and lifestyle factors influence the risk of developing dementia. Diet is one of the modifiable lifestyle factors thought to affect risk, but it is unclear whether there is an interplay with genetic risk factors in relation to incident dementia. Method Data was derived from the population-based Gothenburg H70 Birth Cohort Studies based in Sweden, including 602 dementia-free 70-year-olds (born 1922 or 1930; 64% women) with dietary and genetic data followed for incident dementia until 2016. Two dietary patterns were derived with reduced rank regression analysis, one healthy (e.g., fruits, vegetables, fish) and one western (e.g., full-fat dairy products, refined bread, red and processed meat). Genetic risk was determined by APOE ε4 status and four non-APOE AD-polygenic risk scores (AD-PRSs). Gene-diet interactions in relation to incident dementia were analysed with cox regression models. If an interaction at a p-value threshold of p< 0.20 was detected, stratified analyses were performed. Analyses were adjusted for sex, energy intake, birth year, age at examination, educational level, physical activity level, cardiovascular risk factors and 10 principal components (to correct for population stratification). Result There was an interaction between APOE ε4 status and a healthy and a western dietary pattern in relation to incident dementia (p=0.13 and p=0.07), while no interactions were found between AD-PRSs and dietary patterns. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia (HR 0.77; 95% CI 0.64–0.94, p=0.008) among ε4 non-carriers, but not among ε4 carriers. There was a borderline association between a western dietary pattern and an increased risk of dementia among ε4 carriers (HR 1.25; 95% CI 0.97–1.61, p=0.08), while no association was observed among ε4 non-carriers. Conclusion The results suggest an interplay between APOE ε4 status and adherence to dietary patterns in relation to incident dementia. The findings from this study could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia incidence.
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| 307. |
- Samuelsson, Malin, et al.
(författare)
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Transcription factors as targets to block inflammation in neurodegenerative disorder : s
- 2006
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 2:3, Supplement, s. S457-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Accumulating evidence supports the importance of inflammation in neurodegenerative disorders like Alzheimer’s disease (AD). Epidemiological studies have revealed that patients taking anti-inflammatory drugs for conditions like arthritis have a lower prevalence of Alzheimer’s than others. In addition, there are reports that show that inflammation indeed can cause neurodegeneration in vivo. “The glial loop hypothesis” describes the model where surrounding glial cells are activated and produce neurotoxic products and therefore lead to neuronal death. One of the most important transcription factors involved in the inflammatory signalling cascade is NF-κB (nuclear factor κB). Supporting a role for NF-κB in AD, this transcription factor has been shown to be upregulated in brains from patients suffering from the disease. Another transcription factor family, thought to work together with NF-κB, is CCAAT enhancer binding protein (C/EBP). C/EBPδ has also been shown to be overexpressed in brains from Alzheimer patients. Objective: Our aim was to characterize the activation of transcription factors that may be involved in AD and to investigate the possibilities to block the effects of these transcription factors. Methods: We have used a delivery system that we have previously developed with a decoy non-covalently bound to a cell-penetrating peptide (CPP). In our studies primary mixed glial cultures from rat (5-10% microglia and 90-95% astrocytes) were used as a modelsystem. Transcription factor activation and cytokine mRNA expression were analyzed by electrophoretic mobility shift assay and RT-PCR, respectively. Cellular uptake studies were performed using confocal laser scanning microscopy. Results: Our studies show that a β-amyloid peptide alone or in combination with the inflammatory cytokine interleukin-1β upregulates NF-κB binding activity as well as the mRNA expression of its downstream target gene interleukin-6 (IL-6). Using our delivery system with an NF-κB decoy resulted in inhibition of upregulated NF-κB binding activity by approx. 80% and IL-6 mRNA expression by approx. 50%. We observed a clear uptake of the CPP-coupled decoy. In parallel, we have also investigated the possibility to use C/EBP as a therapeutic target. Conclusion: Facilitated uptake of transcription factor decoys may be a promising strategy to target the inflammation in neurodegenerative disorders like AD.
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| 308. |
- Sanchez, Erlan, et al.
(författare)
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Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
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| 309. |
- Sandelius, Åsa P, et al.
(författare)
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Elevated CSF GAP-43 is Alzheimer's disease specific and associated with tau and amyloid pathology.
- 2019
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 15:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection.We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies.GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology.The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.
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| 310. |
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