A comparative assessment of γ-secretase activity in transgenic and non-transgenic rodent brain

Pharmacological Assessment of <i>γ</i>-Secretase Activity from Rodent and Human Brain

“…An in vitro assay to measure γ-secretase activity by measuring the de novo production of Aβ40 has been described previously [35,36] using γ-secretase enriched membranes derived from HeLa cells following the addition of a C-terminal fragment of APP as an exogenous source of substrate. Although several investigators have reported the use of γ-secretase derived from rodent or human brain [38,[42][43][44], to our knowledge there are no reports that compare the pharmacological activity of γ-secretase inhibitors and modulators in brain membranes that are prepared from multiple species, including human brain tissue, nor do these reports measure Aβ42 generation. Here we describe a rapid and facile protocol for the partial purification of a γ-secretase complex from brain Table 1.…”