formation of A4

^[1]^[2]

Introduction

Formation of A4:

coordinate activity of beta- & gamma-secretases result in formation of A4 (see membrane region of APP)
regulation by cholesterol & cholesterol esters
- formation of A4 in cultured neurons is increased by addition of cholesterol to the medium^[1]
- lovastatin reduces A4 in plasma of human patients
- statins diminish beta- & gamma-secretase activity in cultured cells^[1]
- statins increase alpha-secretase activity in cultured cells^[1]
- A4 production in cultured cells depends on cholesterol ester levels not on total cholesterol^[1]
- inhibition of acyl-cholesterol acyltransferase (ACAT) diminishes A4 production^[1]
in animal models, some NSAIDs diminished A4/42 production
- NSAIDS that diminished A4/42 production^[2]
  - ibuprofen#, indomethacin#, sulindac
- NSAIDS that did NOT diminish A4/42 production
  - aspirin, naproxen, celecoxib

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 Marx J. Science 294:509, 2001
↑ ^2.0 ^2.1 Journal Watch 21(24):194, 2001 Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001 Nov 8;414(6860):212-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11700559