| 211. |
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| 212. |
- Winblad, Bengt, et al.
(författare)
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Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study.
- 2012
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Ingår i: Lancet neurology. - 1474-4465. ; 11:7, s. 597-604
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy targeting the amyloid β (Aβ) peptide is a potential strategy to slow the progression of Alzheimer's disease. We aimed to assess the safety and tolerability of CAD106, a novel active Aβ immunotherapy for patients with Alzheimer's disease, designed to induce N-terminal Aβ-specific antibodies without an Aβ-specific T-cell response.
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| 213. |
- Winblad, Kjell, et al.
(författare)
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Lock-free Contention Adapting Search Trees
- 2018
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Ingår i: The 30th ACM Symposium on Parallelism in Algorithms and Architectures, SPAA 2018. - New York, NY, USA : ACM. - 9781450357999
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Konferensbidrag (refereegranskat)
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| 214. |
- Winblad, Kjell, et al.
(författare)
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Lock-free Contention Adapting Search Trees
- 2021
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Ingår i: ACM TRANSACTIONS ON PARALLEL COMPUTING. - : Association for Computing Machinery (ACM). - 2329-4949 .- 2329-4957. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Concurrent key-value stores with range query support are crucial for the scalability and performance ofmany applications. Existing lock-free data structures of this kind use a fixed synchronization granularity. Using a fixed synchronization granularity in a concurrent key-value store with range query support is problematic as the best performing synchronization granularity depends on a number of factors that are difficult to predict, such as the level of contention and the number of items that are accessed by range queries. We present the first linearizable lock-free key-value store with range query support that dynamically adapts its synchronization granularity. This data structure is called the lock-free contention adapting search tree (LFCA tree). An LFCA tree automatically performs local adaptations of its synchronization granularity based on heuristics that take contention and the performance of range queries into account. We show that the operations of LFCA trees are linearizable, that the lookup operation is wait-free, and that the remaining operations (insert, remove and range query) are lock-free. Our experimental evaluation shows that LFCA trees achieve more than twice the throughput of related lock-free data structures in many scenarios. Furthermore, LFCA trees are able to perform substantially better than data structures with a fixed synchronization granularity over a wide range of scenarios due to their ability to adapt to the scenario at hand.
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| 215. |
- Xu, Weili, et al.
(författare)
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Accelerated progression from mild cognitive impairment to dementia in people with diabetes
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:11, s. 2928-35
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia.RESEARCH DESIGN AND METHODS: In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI] and 182 with other cognitive impairment no dementia [oCIND]) age ≥ 75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥ 11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8-11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models.RESULTS: During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30-6.34) for diabetes, and 4.96 (2.27-10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI.CONCLUSIONS: Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.
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| 216. |
- Xu, Wei-Li, et al.
(författare)
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Accelerated Progression from Mild Cognitive Impairment to Dementia Among APOE epsilon 4 epsilon 4 Carriers
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:2, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- The impact of APOE ε4 on mild cognitive impairment (MCI) and its progression to dementia remain controversial. We aimed to examine the association of APOE ε4 with MCI, and to verify the hypothesis that ε4 accelerates progression from MCI to dementia. In the Kungsholmen project, 756 cognitively healthy participants and 212 people with MCI aged ≥75 years were identified at baseline. Amnestic MCI (aMCI) and other cognitive impairment no dementia (oCIND) as two subtypes of MCI were assessed based on standard definitions. The two cohorts were followed for 9 years to detect incident cases of MCI and dementia following international criteria. APOE genotypes were assessed at baseline. Data were analyzed using Cox models. During the follow-up, in the cognitively healthy cohort, 165 people developed MCI (40 aMCI and 125 oCIND) and 176 developed dementia; in the MCI cohort, 118 persons progressed to dementia. Compared with APOE ε3ε3, the hazard ratios (HRs) (95% CIs) of ε2ε4/ε3ε4 were 2.24 (1.10-4.57) for aMCI and 1.78 (1.15-2.75) for oCIND, while the ε4ε4 was related to dementia with a HR of 4.35 (1.97-9.63) in the cognitively healthy cohort. In the MCI cohort, the ε4ε4 genotype led to a multi-adjusted HR of 2.89 (1.12-7.48) for dementia and accelerated the progression to dementia by 3.36 years. The APOE ε4 heterozygotes are associated with an increased risk of aMCI and oCIND. The ε4 homozygote substantially accelerates progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI.
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| 217. |
- Xu, Wei-Li, et al.
(författare)
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HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease : A Population-Based Longitudinal Study
- 2015
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged >= 75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged >= 60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19-2.32) and 1.66 (95% CI 1.06-2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.407.18) and 4.81 (95% CI 1.88-8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63-8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45-9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04-2.99) and 1.64 (1.02-2.33) for the diabetes-AD and dementia-AD associations, respectively, and 4.06 (95% CI 1.06-7.58, p = 0.039) and 3.29 (95% CI 1.02-8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.
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| 218. |
- Yu, Yang, et al.
(författare)
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Neuronal A beta 42 is enriched in small vesicles at the presynaptic side of synapses
- 2018
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Ingår i: Life Science Alliance. - : LIFE SCIENCE ALLIANCE LLC. - 2575-1077. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid beta-peptide (A beta) is a physiological ubiquitously expressed peptide suggested to be involved in synaptic function, long-term potentiation, and memory function. The 42 amino acid-long variant (A beta 42) forms neurotoxic oligomers and amyloid plaques and plays a key role in the loss of synapses and other pathogenic events of Alzheimer disease. Still, the exact localization of A beta 42 in neurons and at synapses has not been reported. Here, we used super-resolution microscopy and show that A beta 42 was present in small vesicles in presynaptic compartments, but not in postsynaptic compartments, in the neurites of hippocampal neurons. Some of these vesicles appeared to lack synaptophysin, indicating that they differ from the synaptic vesicles responsible for neurotransmitter release. The A beta 42-containing vesicles existed in presynapses connected to stubby spines and mushroom spines, and were also present in immature presynapses. These vesicleswere scarce inother parts of the neurites, where A beta 42 was instead present in large, around 200-600 nm, vesicular structures. Three-dimensional super-resolution microscopy confirmed that A beta 42 was present in the presynapse and absent in the postsynapse.
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| 219. |
- Zhou, Robin Ziyue, et al.
(författare)
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A glycan epitope correlates with tau in serum and predicts progression to Alzheimer's disease in combination with APOE4 allele status
- 2023
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:7, s. 3244-3249
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is an urgent need for novel blood biomarkers for the detection of Alzheimer's disease (AD). We previously showed that levels of the bisecting N-acetylglucosamine glycan epitope was elevated in cerebrospinal fluid in AD. However, its diagnostic value in blood is unknown.METHODS: We analyzed blood levels of bisecting N-acetylglucosamine and total tau in a retrospective cohort of 233 individuals. Progression to AD was compared between the groups using Cox regression. The predictive value of the biomarkers was determined by logistic regression.RESULTS: Bisecting N-acetylglucosamine correlated with tau levels (p < 0.0001). Individuals with an intermediate tau/bisecting N-acetylglucosamine ratio had elevated AD risk (hazard ratio = 2.06, 95% confidence interval [CI]: 1.18–3.6). Moreover, a combined model including tau/bisecting N-acetylglucosamine ratio, apolipoprotein E (APOE) ε4 status, and Mini-Mental State Examination score predicted future AD (area under the curve = 0.81, 95% CI: 0.68–0.93).DISCUSSION: Bisecting N-acetylglucosamine in combination with tau is a valuable blood biomarker for predicting AD.
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| 220. |
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