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Sökning: WFRF:(Johannsen Peter) > Linköpings universitet

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1.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
  • 2018
  • Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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2.
  • Wallgren, Jakob, 1987- (författare)
  • An insight into the metabolism of New Psychoactive Substances : Structural elucidation of urinary metabolites of synthetic cannabinoids and fentanyl analogues using synthesized reference standards
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • New Psychoactive Substances (NPS) is an umbrella term covering hundreds of substances across different drug groups. Many of these substances were originally developed for therapeutic use but have later appeared on the recreational drug market. The use of NPS has been associated with many outbreaks leading to hospitalizations and has been implicated in numerous fatalities worldwide. To be able to analytically detect drugs in a forensic setting is vital in the fight against the abuse of NPS. One of the most notable challenges in detection of NPS is the identification of major urinary metabolites for use as biomarkers. Furthermore, given the lack of reference standards in most metabolism studies, the major urinary metabolites can often only be tentatively determined.This thesis describes the synthesis and analysis of potential metabolites used to identify the exact structures of major metabolites of the synthetic cannabinoid AKB-48, fentanyl and five fentanyl analogues in authentic human urine samples and/or hepatocyte incubations. Synthetic targets were chosen based on previous metabolism studies by our research group. Subsequently, synthetic routes were developed to produce numerous potential metabolites across the studied NPS. The synthesized reference standards were analyzed by LC-QTOF-MS alongside hepatocyte drug incubations and authentic human urine samples. Comparison of the resulting analytical data was used to determine the exact structures of many metabolites. This includes urinary metabolites of AKB-48 with a single hydroxyl group situated on a secondary carbon of the adamantane moiety, or position 3 or 5 of the pentyl side chain. For the studied fentanyls, the β-OH and the 4’-OH metabolites were abundant metabolites identified in hepatocyte incubations while the 4’-OH, 4’-OH-3’-OMe and 3’,4’-diOH were the favored metabolic motifs among the metabolites identified in urine.Additionally, a concise synthetic route to produce synthetic cannabinoid metabolites with the 4-OH-5F pentyl side chain motif was developed and demonstrated for four synthetic cannabinoids.       These findings and the developed synthetic routes can be used to provide forensic toxicology laboratories with urinary biomarkers for drug detection. Moreover, the synthesized reference standards of major metabolites can be studied to better understand the toxicity of their parent drugs.
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