Chapter 24. Amyloidogenesis as a Therapeutic Target in Alzheimer's Disease

Barry D. Greenberg, Ference J. Kezdy, Robert Kisilevsky

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is a progressive degenerative encephalopathy associated with behavioral disorders, loss of memory and personality, physical debility, and, ultimately, death. It is the most common cause of dementia. While AD is an amyloidosis of the brain, it has been shown that neurotransmitter deficits more closely mirror the degree of dementia than the level of amyloidotic deposits in the AD brains. There is a case-to-case heterogeneity of the disease process, differences in diagnostic reliability among clinical centers, and complex interactions among various neurotransmitter systems within the brain. Because neuronal death is cumulative in AD, neurotic loss and neurotransmitter deficits are expected to increase progressively. Measures of plaque and tangle density reflect net formation and removal, as suggested in the only published pseudotime course study of AD. Therefore, the rate of amyloid plaque and neurofibrillary tangle (NFT) formation should plateau as the neurons responsible for the synthesis of their precursors die. Amyloid deposition is likely a participant in the progression of AD-associated neural degeneration. Amelioration of amyloid-related pathology may prove therapeutically promising, because this approach addresses all the various transmitter deficits and the neuronal degeneration responsible for dementia. This chapter discusses Alzheimer amyloid, amino acid permease (AAP) gene and transcripts, AAP synthesis and distribution, the processing and function of AAP protein, AD amyloidogenesis, and its therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalAnnual Reports in Medicinal Chemistry
Volume26
Issue numberC
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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