SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Lautner Ronald) "

Sökning: WFRF:(Lautner Ronald)

  • Resultat 1-10 av 19
  • [1]2Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Lautner, Ronald, et al. (författare)
  • Biomarkers for microglial activation in Alzheimer's disease.
  • 2011
  • Ingår i: International journal of Alzheimer's disease. - 2090-0252. ; 2011
  • Tidskriftsartikel (refereegranskat)abstract
    • Intensive research over the last decades has provided increasing evidence for neuroinflammation as an integral part in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Inflammatory responses in the central nervous system (CNS) are initiated by activated microglia, representing the first line of the innate immune defence of the brain. Therefore, biochemical markers of microglial activation may help us understand the underlying mechanisms of neuroinflammation in AD as well as the double-sided qualities of microglia, namely, neuroprotection and neurotoxicity. In this paper we summarize candidate biomarkers of microglial activation in AD along with a survey of recent neuroimaging techniques.
  •  
2.
  • Lautner, Ronald, et al. (författare)
  • Preclinical effects of APOE ϵ4 on cerebrospinal fluid Aβ42 concentrations
  • 2017
  • Ingår i: Alzheimer's Research and Therapy. - BioMed Central (BMC). - 1758-9193. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: From earlier studies it is known that the APOE ϵ2/ϵ3/ϵ4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD. Methods: APOE genotype and CSF Aβ42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17-99 from nine different clinical research centers. Results: CSF concentrations of Aβ42 were lower in APOE ϵ4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE ϵ4 on CSF Aβ42 was age dependent. The age at which CSF Aβ42 concentrations started to decrease was estimated at 50 years in APOE ϵ4-negative individuals and 43 years in heterozygous APOE ϵ4 carriers. Homozygous APOE ϵ4 carriers showed a steady decline in CSF Aβ42 concentrations with increasing age throughout the examined age span. Conclusions: People possessing the APOE ϵ4 allele start to show a decrease in CSF Aβ42 concentration almost a decade before APOE ϵ4 noncarriers already in early middle age. Homozygous APOE ϵ4 carriers might deposit Aβ42 throughout the examined age span. These results suggest that there is an APOE ϵ4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
3.
  • Mattsson, Niklas, et al. (författare)
  • Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease
  • 2018
  • Ingår i: Neurobiology of Aging. - Elsevier. - 0197-4580. ; 71, s. 81-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.
  •  
4.
  • Olsson, Bob, et al. (författare)
  • Microglial markers are elevated in the prodromal phase of Alzheimer's disease and vascular dementia.
  • 2013
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 33:1, s. 45-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Microglia manage immunosurveillance and mediate inflammation, both suggested to be important in Alzheimer's disease (AD). The aim of this study was to investigate if microglial markers could differentiate, firstly between AD and controls, and secondly between stable mild cognitive impairment (MCI) and those progressing to AD and vascular dementia (VaD). Furthermore, we investigated if these markers were sufficiently stable to be used in clinical trials. We quantified YKL-40 and sCD14 in cerebrospinal fluid (CSF) from 96 AD patients, 65 healthy controls, and 170 patients with MCI from baseline and over 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six-month interval in between. YKL-40, but not sCD14, was significantly elevated in AD compared with healthy controls (p=0.003). Furthermore, YKL-40 and sCD14 were increased in MCI patients who converted to VaD (p=0.029 and p=0.008), but not to AD according to NINCDS-ADRDA. However, when stratified according to CSF levels of tau and A beta(42), YKL-40 was elevated in those with an AD-indicative profile compared with stable MCI with a normal profile (p=0.037). In addition, YKL-40 and sCD14 were very stable in AD patients with good correlation between time-points (r=0.94, p=3.4x10(-25); r=0.77, p=2.0x10(-11)) and the cortical damage marker T-tau. Thus, microglial markers are stable and may be used as safety markers for monitoring CNS inflammation and microglia activation in clinical trials. Moreover, YKL-40 differentiates between AD and controls and between stable MCI and those that convert to AD and VaD.
  •  
5.
  • Skillbäck, Tobias, et al. (författare)
  • Apolipoprotein E genotypes and longevity across dementia disorders
  • 2018
  • Ingår i: Alzheimer's and Dementia. - Wiley. - 1552-5260. ; 14:7, s. 895-901
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied. Methods: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity. Results: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P =.006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P =.028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders. Discussion: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.
  •  
6.
  •  
7.
  • Daborg, Jonny, et al. (författare)
  • Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer's disease.
  • 2012
  • Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - 1435-1463. ; 119:7, s. 789-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is strongly associated with loss of synapses. The complement system has been shown to be involved in synaptic elimination. Several studies point to an association between AD and the complement system. The purpose of this study was to examine the association of cerebrospinal fluid (CSF) levels of complement components 3 and 4 (C3 and C4, respectively), and complement receptor 1 (CR1) with AD in 43 patients with AD plus dementia, 42 patients with mild cognitive impairment (MCI) who progressed to AD during follow-up (MCI-AD), 42 patients with stable MCI and 44 controls. Complement levels were also applied in a multivariate model to determine if they provided any added value to the core AD biomarkers A beta 42, T-tau and P-tau. We found elevated CSF levels of C3 and C4 in AD compared with MCI without progression to AD, and elevated CSF levels of CR1 in MCI-AD and AD when these groups were merged. These results provide support for aberrant complement regulation as a part in the AD process, but the changes are not diagnostically useful.
  •  
8.
  • Gren, Magnus, et al. (författare)
  • Blood biomarkers indicate mild neuroaxonal injury and increased amyloid <em>β </em>production after transient hypoxia during breath-hold diving
  • 2016
  • Ingår i: Brain Injury. - Taylor & Francis. - 0269-9052 .- 1362-301X. ; 30:10, s. 1226-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objective:</strong> To determine whether transient hypoxia during breath-hold diving causes neuronal damage or dysfunction or alters amyloid metabolism as measured by certain blood biomarkers.</p><p><strong>Design:</strong> Sixteen divers competing in the national Swedish championship in breath-hold diving and five age-matched healthy control subjects were included. Blood samples were collected at baseline and over a course of 3 days where the divers competed in static apnea (STA), dynamic apnea without fins (DYN1) and dynamic apnea with fins (DYN2).</p><p><strong>Main outcomes:</strong> Biomarkers reflecting brain injury and amyloid metabolism were analysed in serum (S-100<em>β</em>, NFL) and plasma (T-tau, A<em>β</em>42) using immunochemical methods.</p><p><strong>Results:</strong> Compared to divers’ baseline, A<em>β</em>42 increased after the first event of static apnea (<em>p</em> = 0.0006). T-tau increased (<em>p</em> = 0.001) in STA vs baseline and decreased after one of the dynamic events, DYN2 (<em>p</em> = 0.03). Further, T-tau correlated with the length of the apneic time during STA (<em>ρ</em> = 0.7226, <em>p</em> = 0.004) and during DYN1 (<em>ρ</em> = 0.66, <em>p</em> = 0.01).</p><p><strong>Conclusion:</strong> The findings suggest that transient hypoxia may acutely increase the levels of A<em>β</em>42 and T-tau in plasma of healthy adults, further supporting that general hypoxia may cause mild neuronal dysfunction or damage and stimulate A<em>β</em> production.</p>
  •  
9.
  •  
10.
  • Lautner, Ronald, et al. (författare)
  • Apolipoprotein e genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.
  • 2014
  • Ingår i: JAMA psychiatry. - 2168-6238. ; 71:10, s. 1183-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 19
  • [1]2Nästa
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy