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1.
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2.
  • Vergallo, A., et al. (författare)
  • Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
  • 2019
  • Ingår i: Alzheimers & Dementia. - 1552-5260. ; 15:6, s. 764-775
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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3.
  • Duits, Flora H, et al. (författare)
  • The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
  • 2014
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Elsevier. - 1552-5279 .- 1552-5260. ; 10:6, s. 713-723
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-ß1-42 (Aβ42), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD).
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4.
  • Rydberg Sterner, Therese, et al. (författare)
  • The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
  • 2019
  • Ingår i: European journal of epidemiology. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
  • Tidskriftsartikel (refereegranskat)abstract
    • To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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5.
  • Wiig, E. H., et al. (författare)
  • The stability of AQT processing speed, ADAS-Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer's disease
  • 2010
  • Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 1600-0404 .- 0001-6314. ; 121:3, s. 186-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives - To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer's disease (AD). Materials and methods -Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and MMSE were administered concurrently. Results-Correlations (rho) between age and AQT processing speed were non-significant, but were significant for ADAS-Cog and Mini Mental State Examination (MMSE). AQT and ADAS-Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman's rho) were moderate-to-high for all tests. Means for subgroups did not differ as a function of medication type. Conclusions - AQT processing speed, ADAS-Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.
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6.
  • Anckarsäter, Rolf, 1956, et al. (författare)
  • Cerebrospinal fluid protein reactions during non-neurological surgery.
  • 2007
  • Ingår i: Acta neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 115:4, s. 254-9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. SUBJECTS AND METHODS: Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. RESULTS: Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (beta2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (betaTP) remained unchanged. CONCLUSIONS: Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.
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7.
  • Lehmann-Werman, Roni, et al. (författare)
  • Identification of tissue-specific cell death using methylation patterns of circulating DNA.
  • 2016
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490 .- 0027-8424. ; 113:13, s. E1826-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.
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8.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Age and diagnostic performance of Alzheimer disease CSF biomarkers.
  • 2012
  • Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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9.
  • Wang, Li-San, et al. (författare)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • Ingår i: JAMA neurology. - 2168-6157. ; 72:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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