Premium
Commentary: “Ceramide and cholesterol: Possible connections between normal aging of the brain and Alzheimer's disease. Just hypotheses or molecular pathways to be identified?” by Claudio Costantini, Rekha M.K. Kolasani, Luigi Puglielli
Author(s) -
Granholm AnnCharlotte,
Bachman David,
Mintzer Jacobo,
Sambamurti Kumar
Publication year - 2005
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2005.06.010
Subject(s) - south carolina , gerontology , columbia university , library science , psychology , medicine , sociology , media studies , political science , computer science , public administration
p e C r g s b t f n l c m t T c p N a c a This excellent review by Costantini et al brings together series of divergent biological processes that occur during ormal aging into an elegant hypothesis for the pathogeneis of Alzheimer’s disease (AD). As correctly noted by ostantini and collaborators, it has been suggested that lterations in dietary lipids may play an important role in ognitive deficits in AD, secondary to their effects on neuonal membrane lipids [1,2]. Most importantly, 2 genetic inks between cholesterol and AD have given reasonable roof that this risk factor must be taken seriously. Apolioprotein E is the main cholesterol transport protein inolved in cholesterol recycling in the brain [3]. There are 3 ifferent alleles ( 2, 3, and 4) of ApoE, of which, the 4 llele is overrepresented among AD patients [4]. It has been ostulated that this risk factor comes into play because of a educed capability for cholesterol reuptake in the brain. urther proof for a role of cholesterol in AD came recently hen investigators found a genetic link between the choesterol-converting enzyme Cyp46 and incidence of AD [5]. yp46, a brain-specific enzyme, acts by regulating the elimnation of excess cholesterol in the brain by adding a hyroxyl group to the cholesterol molecule, producing a prodct that is more soluble than cholesterol and able to be xported from the brain. Several different investigators [5,6] ave reported that patients with a Cyp46 polymorphism, xhibit an increase in the plaque load as well as an increase n cerebrospinal fluid (CSF) Ab42. Thus, there are several linical indications that cholesterol plays a role in AD, but biological mechanism for this influence has not been fully nderstood. In animal models, it has also been shown unquivocally that high cholesterol and high-fat diets affect