P4–286: Secretion of the soluble APP ectodomain (APPS) is not affected by the non–steroidal anti–inflammatory drugs ibuprofen and indomethacin in primary neuronal cultures

Nonsteroidal Anti-Inflammatory Drugs and Ectodomain Shedding of the Amyloid Precursor Protein

<i>Background:</i> Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer’s disease (AD). Several mechanisms have been proposed to explain these findings including increased shedding of the soluble ectodomain of the amyloid precursor protein (sAPP), which functions as a neurotrophic and neuroprotective factor in vitroand in vivo. <i>Objective:</i> To clarify whether NSAIDs consistently stimulate sAPP secretion. <i>Methods:</i> 293-EBNA cells with stable overexpression of an APP-alkaline phosphatase fusion protein (APP-AP), SH-SY5Y and PC12 cells or prim…

New pathways of increased cardiovascular risk in depression: a pilot study on the association of high-sensitivity C-reactive protein with pro-atherosclerotic markers in patients with depression.

Abstract Background An elevation of inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) can be found in patients with depressive disorders. Inflammatory processes are known to influence atherosclerosis and might also mediate the link between depression and diabetes. The present study aimed at comparing hs-CRP and its relationship with atherogenic platelet markers in patients with type 2 diabetes (TD2) and/or newly diagnosed major depression (MD). Methods Hs-CRP concentrations in 24 patients with TD2, 21 patients with MD (diagnosed according to ICD-10 and DSM-IV), 19 patients with TD2 and comorbid MD, and 25 healthy controls were compared using analysis of variance. The…

Independent Generation of Aβ42 and Aβ38 Peptide Species by γ-Secretase

Proteolytic processing of the amyloid precursor protein by beta- and gamma-secretase generates the amyloid-beta (Abeta) peptides, which are principal drug targets in Alzheimer disease therapeutics. gamma-Secretase has imprecise cleavage specificity and generates the most abundant Abeta40 and Abeta42 species together with longer and shorter peptides such as Abeta38. Several mechanisms could explain the production of multiple Abeta peptides by gamma-secretase, including sequential processing of longer into shorter Abeta peptides. A novel class of gamma-secretase modulators (GSMs) that includes some non-steroidal anti-inflammatory drugs has been shown to selectively lower Abeta42 levels withou…

German validation of the conners adult ADHD rating scale-self-report: confirmation of factor structure in a large sample of participants with ADHD.

Objective: The Conners Adult ADHD Rating Scales (CAARS) assess symptoms specific to adults that are frequently used and have been translated into German. The current study tests the factor structure of the CAARS in a large sample of German adults with ADHD and compares the means of the CAARS subscales with those of healthy German participants. Method: CAARS were completed by 466 participants with ADHD and 851 healthy control participants. Confirmatory factor analysis was used to establish model fit with the American original. Comparisons between participants with ADHD and healthy controls and influences of gender, age, and degree of education were analyzed. Results: Confirmatory factor anal…

Einfluss von multimodaler sportlicher Aktivität auf Kognition und Alltagskompetenzen bei früher Alzheimer-Demenz (SPORT&KOG)

Der vorliegende Bericht beschreibt ein vom Bundesministerium für Gesundheit gefördertes Vorhaben zum «Leuchtturmprojekt Demenz» im Themenfeld 1 «Therapie und Pflegemaßnahmen: Wirksamkeit unter Alltagsbedingungen». Hierbei handelt es sich um eine multizentrische randomisierte Interventionsstudie, die den Einfluss von Sport (multimodale sportliche Aktivität) unter kontrollierten Bedingungen auf die kognitive Entwicklung von Alzheimer-Patienten im frühen Stadium prüft. In einem zweiarmigen Design werden je 150 Patienten mit früher AD unter Verum- bzw. Kontroll-Bedingungen untersucht. Die Verum-Gruppe erhält ein spezifisches sportliches Trainingsprogramm. In der Kontrollgruppe werden lediglich…

German validation of the Conners Adult ADHD Rating Scales (CAARS) II: reliability, validity, diagnostic sensitivity and specificity.

AbstractBackgroundThe German version of the Conners Adult ADHD Rating Scales (CAARS) has proven to show very high model fit in confirmative factor analyses with the established factors inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional lability, and problems with self-concept in both large healthy control and ADHD patient samples. This study now presents data on the psychometric properties of the German CAARS-self-report (CAARS-S) and observer-report (CAARS-O) questionnaires.MethodsCAARS-S/O and questions on sociodemographic variables were filled out by 466 patients with ADHD, 847 healthy control subjects that already participated in two prior studies, and a tota…

P4‐192: Mechanism of γ‐secretase cleavage: Evidence for independent generation of Aβ42 and Aβ38 peptide species