Find results with:

Add another field

Search by date

to

Searching collections:

Dartmouth Dissertations

Add or remove collections

Home Dartmouth Dissertations Page 1

Reference URL

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Genetic inactivation of ACAT1 ameliorates the amyloid pathology and cognitive deficits in a mouse model of Alzheimer's disease.

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Call No.	QP606.A33 B79 2008
Author	Bryleva, Elena Yurevna.
Title	Genetic inactivation of ACAT1 ameliorates the amyloid pathology and cognitive deficits in a mouse model of Alzheimer's disease.
Date	2008
Abstract	Acyl-CoA:Cholesterol Acyltransferases (ACATs) are key enzymes in cellular cholesterol metabolism. ACAT converts free cholesterol to cholesterol ester, which makes it more easily storable in lipid droplets. There are two ACAT genes encoding two different enzymes (ACAT1 and ACAT2). Both enzymes are potential targets for treating dyslipidemia and atherosclerosis. While the roles of ACAT1/ACAT2 have been extensively studied in various systemic tissues, their expressions and the roles in the central nervous system under normal and pathological conditions have not been thoroughly studied. Recently Kovacs and colleagues discovered that administration of specific ACAT inhibitors markedly reduces amyloid-β (Aβ) accumulation in the brains of a transgenic mouse model for Alzheimer's disease (AD), and rescues the loss of cognitive function. In order to examine the specificity of the ACAT inhibitor and to determine which of the ACAT isoforms affects the AD's progression, we crossed a triple transgenic Alzheimer's mouse model (3x-Tg-AD) to the ACAT1 or ACAT2 knock-out mice. Our immunohistochemical and biochemical data show that the levels of human tau, human APP and its proteolytic fragments are significantly decreased in the brains of ACAT1-/-/Alzheimer's (ACAT1-/-/Alz) mice when compared to the control Alzheimer's (ACAT1+/+/Alz) mice. Additional analyses by ELISA and by thioflavin S staining of the 12 months old mice show that ACAT1 deficiency significantly decreased the Aβ40 and Aβ42 load as well as amyloid plaques in the hippocampus, the region important in memory formation. Finally we demonstrate through contextual fear conditioning behavioral study that ACAT1 deficiency rescued the cognitive decline manifested in the 3x-Tg-AD mice. In conclusion, our results show that ACAT1 inactivation delays the progression of AD in a 3x-Tg-AD mouse model of AD, and suggest that ACAT1 is a potential target for treating AD.
Description	xiv, 185 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Ta-Yuan Chang
Subject	Acyltransferases -- Genetic aspects. Enzyme inhibitors. Alzheimer's disease. Amyloid.
College	Dartmouth Medical School -- Department of Biochemistry.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.188

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Genetic Inactivation of ACAT1 Ameliorates the Amyloid Pathology and Cognitive Deficits in a Mouse Model of Alzheimer's Disease A Thesis Submitted to the Faculty In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry by Elena Yurevna Bryleva DARTMOUTH COLLEGE Hanover, New Hampshire May 27, 2008 Examining Committee: ______________________ (chair) William F. Hickey, M.D. ____________________________ Brent T. Harris, M.D., Ph.D. ____________________________ Barbara Tate, Ph.D. ____________________________ Ta-Yuan Chang, Ph.D. ____________________________ Charles K. Barlowe, Ph.D. Dean of Graduate Studies

Find results with:

Searching collections:

Home Dartmouth Dissertations Page 1

Genetic inactivation of ACAT1 ameliorates the amyloid pathology and cognitive deficits in a mouse model of Alzheimer's disease.

Object Description

Description

Genetic inactivation of ACAT1 ameliorates the amyloid...

Genetic inactivation of ACAT1 ameliorates the amyloid...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12