19 October 2004. Inhibiting ACAT, a cholesterol-modifying
enzyme, may prove a viable therapy for preventing or slowing the
progression of Alzheimer disease, according to a report in the
October 14 Neuron. A multi-institution collaboration led by Dora
Kovacs at Massachusetts General Hospital, Boston, shows that
inhibiting the enzyme limits production of amyloid-β (Aβ),
reduces plaque load, and prevents learning and memory losses in
a mouse model of the disease. ACAT (Acyl coenzyme A: cholesterol
transferase) catalyzes the esterification of cholesterol,
redistributing the lipid from the plasma membrane into
cytoplasmic droplets. Kovacs and colleagues have previously
reported that blocking the enzyme attenuates production of Aβ in
primary neurons (see ARF related news story). Now, joint first
authors Birgit Hutter-Paier at JSW-Research Forschungslabor
GmbH, Graz, Austria, and Henri Huttunen at MGH, along with other
researchers from these institutions and the Mayo Clinic,
Jacksonville, Florida, extend those obser