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Mechanism for β-amyloid Overproduction in Alzheimer Disease

Possible Antisense RNA-mediated Generation of a 5′-truncated βAPP MRNA Encoding 12-kDa C-terminal Fragment of βAPP, the Immediate Precursor of Aβ
  • Vladimir Volloch
Chapter
Part of the Contemporary Neuroscience book series (CNEURO)

Abstract

The overproduction of p-amyloid (AP) is associated with and appears to be a primary cause of Alzheimer’s disease (AD). Aβ can be generated by proteolysis of p-amyloid precursor protein (βAPP) in both AD-affected and normal cells. There is no evidence, however, that proteolytic cleavage leading to the production of AP in sporadic AD-affected and in normal tissues differs qualitatively or quantitatively to account for the overproduction of Aβ in AD. Therefore, an additional pathway for the enhanced production of Aβ may be involved in sporadic AD. A mechanism is proposed that may be responsible for the overproduction of Aβ in sporadic AD, which constitutes the majority of all AD cases. The proposed mechanism, which may be activated or enhanced in sporadic AD-affected tissues, is based on a model for cellular mRNA replication developed in the author’s laboratory and proposes the antisense RNA-mediated generation of a 5’-truncated βAPP mRNA encoding 12-kDa C-terminal fragment of βAPP, the immediate precursor of Aβ, followed by initiation of translation at met596 contiguously preceding Ap. The proposed model makes several verifiable predictions and suggests new directions of experimentation that may lead to a better understanding of the mechanisms involved in AD. It also sheds a new light on some previously unexplained results in the field of AD.

Keywords

Alzheimer Disease Down Syndrome Antisense Strand Globin mRNA Complementary Element 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 1997

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  • Vladimir Volloch

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