Abstract/Details

Towards a better understanding of Alzheimer's disease: N -terminally truncated Aβ species and Alzheimer's disease pathogenesis


2005 2005

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Abstract (summary)

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Aging is the major risk factor for AD. Nearly 50% of people over the age of 85 are likely to be affected by AD (3). As the general population of the United States and other developed countries ages, Alzheimer's disease is becoming a global health and social crisis. Recent statistics indicate that 4.5 million Americans have Alzheimer's disease and 13 million could be affected by the year 2050 (4). A better understanding of the disease mechanism is crucial for developing a specific and effective intervention. Extensive studies have been performed to understand the pathological hallmarks of AD: extracellular amyloid plaques, which contain amyloid β peptides (Aβ); and intracellular neurofibrillary tangles, which contain hyperphosphorylated Tau. This dissertation describes our attempt to understand the role of N-terminally truncated Aβ especially Aβ11-40/42 in the development of AD. This pool of Aβ is not only readily detectable in AD patients' brains, but also could be generated directly by enzymes responsible for generating full length Aβ. Yet, for historical reasons, research efforts have mostly been focused on the generation, distribution and toxicity of full length Aβ. Here we performed a systematic analysis to understand the generation of Aβ11-40/42 in cell lines, their distribution in postmortem human AD/Down syndrome (DS) brain tissues and their toxicity in a transgenic mouse model. Our studies suggest that Aβ11 is an important component of AD pathology, as it is readily secreted by cells and is abundant in postmortem human brain tissues. This calls for further analysis of the role of N-terminally truncated Aβ species in the pathogenesis of AD.

Indexing (details)


Subject
Neurology;
Pathology
Classification
0317: Neurology
0571: Pathology
Identifier / keyword
Health and environmental sciences; Biological sciences; Alzheimer's disease; Amyloid beta-peptide; N-terminally truncated; Pathogenesis
Title
Towards a better understanding of Alzheimer's disease: N -terminally truncated Aβ species and Alzheimer's disease pathogenesis
Author
Liu, Kangning
Number of pages
162
Publication year
2005
Degree date
2005
School code
0175
Source
DAI-B 66/02, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0542006189, 9780542006180
Advisor
Lee, Virginia M-Y
University/institution
University of Pennsylvania
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3165722
ProQuest document ID
305409216
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305409216
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