22:T407,Introducing mutations within the amyloid precursor protein (APP) that affect beta- and gamma-secretase cleavages results in amyloid plaque formation in vivo. However, the relationship between beta-amyloid deposition and the subcellular site of Abeta production is unknown. To determine the effect of increasing beta-secretase (BACE) activity on Abeta deposition, we generated transgenic mice overexpressing human BACE. Although modest overexpression enhanced amyloid deposition, high BACE overexpression inhibited amyloid formation despite increased beta-cleavage of APP. However, high BACE expression shifted the subcellular location of APP cleavage to the neuronal perikarya early in the secretory pathway. These results suggest that the production, clearance, and aggregation of Abeta peptides are highly dependent on the specific neuronal subcellular domain wherein Abeta is generated and highlight the importance of perikaryal versus axonal APP proteolysis in the development of Abeta amyloid pathology in Alzheimer's disease.23:T504,The (-)-trans-Δ⁹-tetrahydrocannabiphorol (Δ⁹-THCP, 1) content of the inflorescence from six Cannabis sativa chemotypes, including 14 plants of distinct genotypes, and two extracts was determined quantitatively via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). This represents the first comprehensive quantitative screening for 1 from various C. sativa chemotypes. Compound 1 was detected in all 13 inflorescence samples originating from "(-)-trans-Δ⁹-tetrahydrocannabinol (Δ⁹-THC, 2) dominant" C. sativa chemotypes, but was not detected in a "cannabidiol (CBD, 3) dominant" chemotype. The inflorescence content of 1 ranged approximately from 0.0023% to 0.0136% (w/w). Comprehensive inflorescence sampling was performed for each specimen investigated. A trend between inflorescence cannabinoid potency and the location of which the inflorescence was sampled on the C. sativa plant was observed for the three cannabinoids tested (1-3). The preliminary results obtained indicate Δ⁹-THCP (1) may have a higher degree of prevalence in C. sativa inflorescence than previously estimated.

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