Role of the beta-amyloid protein in Alzheimer's disease - PubMed (original) (raw)
Review
Role of the beta-amyloid protein in Alzheimer's disease
S S Sisodia et al. FASEB J. 1995 Mar.
Abstract
A major histopathological hallmark of Alzheimer's disease (AD) is the presence of amyloid deposits in the parenchyma of the amygdala, hippocampus, and neocortex. The principal component of amyloid is the beta-amyloid protein (A beta), a 39-43 amino acid peptide composed of a portion of the transmembrane domain and the extracellular domain of the amyloid precursor protein (APP). APP occurs as several A beta-containing isoforms of 695, 751, and 770 amino acids, with the latter two APP containing a domain that shares structural and functional homologies with Kunitz serine protease inhibitors. In cultured cells, APP mature through the constitutive secretory pathway, and some cell surface-bound APP are cleaved by an enzyme, designated as alpha-secretase, within the A beta domain, an event that precludes A beta amyloidogenesis. Several studies have delineated two additional pathways of APP processing: first, an endosomal/lysosomal pathway generates a complex set of APP-related membrane-bound fragments, some of which contain the entire A beta sequence; and, second, by mechanisms which are not fully understood, A beta 1-40 is secreted into the conditioned medium in vitro and is present in cerebrospinal fluid in vivo. The intracellular sites of enzymes responsible for proteolytic cleavage at the NH2 and COOH termini of A beta, termed gamma- and beta-secretase, respectively, have not been identified. Finally, recent molecular genetic investigations have identified a variety of mutations in APP that segregate with early-onset familial AD and with hereditary cerebral hemorrhage with amyloid, Dutch type (HCHWA-D). Several of these mutations appear to influence APP processing and result in the production of higher levels or longer A beta-related peptides that are inherently more fibrillogenic. Although a variety of lines of evidence implicates APP/A beta in AD, the mechanisms by which A beta influences the biology and vulnerability of neural cells are not fully understood but are very active areas of investigation. This review focuses on the present state of our understanding of APP and A beta in the context of AD.
Similar articles
- Amyloid beta amyloidosis in Alzheimer's disease.
Price DL, Sisodia SS, Gandy SE. Price DL, et al. Curr Opin Neurol. 1995 Aug;8(4):268-74. doi: 10.1097/00019052-199508000-00004. Curr Opin Neurol. 1995. PMID: 7582041 Review. - [Alzheimer disease: cellular and molecular aspects].
Octave JN. Octave JN. Bull Mem Acad R Med Belg. 2005;160(10-12):445-9; discussion 450-1. Bull Mem Acad R Med Belg. 2005. PMID: 16768248 French. - Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease.
Rozemuller AJ, Roos RA, Bots GT, Kamphorst W, Eikelenboom P, Van Nostrand WE. Rozemuller AJ, et al. Am J Pathol. 1993 May;142(5):1449-57. Am J Pathol. 1993. PMID: 7684195 Free PMC article. Review. - The role of beta-amyloid in the development of Alzheimer's disease.
Ii K. Ii K. Drugs Aging. 1995 Aug;7(2):97-109. doi: 10.2165/00002512-199507020-00004. Drugs Aging. 1995. PMID: 7579788 Review.
Cited by
- WIMOAD: Weighted Integration of Multi-Omics data for Alzheimer's Disease (AD) Diagnosis.
Xiao H, Wang J, Wan S. Xiao H, et al. bioRxiv [Preprint]. 2024 Sep 27:2024.09.25.614862. doi: 10.1101/2024.09.25.614862. bioRxiv. 2024. PMID: 39386613 Free PMC article. Preprint. - Induced expression of rabies glycoprotein in the dorsal hippocampus enhances hippocampal dependent memory in a rat model of Alzheimer's disease.
Aliakbari S, Hasanzadeh L, Sayyah M, Amini N, Pourbadie HG. Aliakbari S, et al. J Neurovirol. 2024 Jun;30(3):274-285. doi: 10.1007/s13365-024-01221-y. Epub 2024 Jun 28. J Neurovirol. 2024. PMID: 38943023 - Anion Binding to Ammonium and Guanidinium Hosts: Implications for the Reverse Hofmeister Effects Induced by Lysine and Arginine Residues.
Jordan JH, Gibb CLD, Tran T, Yao W, Rose A, Mague JT, Easson MW, Gibb BC. Jordan JH, et al. J Org Chem. 2024 May 17;89(10):6877-6891. doi: 10.1021/acs.joc.4c00242. Epub 2024 Apr 25. J Org Chem. 2024. PMID: 38662908 Free PMC article. - Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer's Disease.
Jaberi S, Fahnestock M. Jaberi S, et al. Biomolecules. 2023 Oct 26;13(11):1577. doi: 10.3390/biom13111577. Biomolecules. 2023. PMID: 38002258 Free PMC article. Review. - Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer's disease by promoting synaptic plasticity of adult-born granule cells.
Ji Q, Yang Y, Xiong Y, Zhang YJ, Jiang J, Zhou LP, Du XH, Wang CX, Zhu ZR. Ji Q, et al. Alzheimers Res Ther. 2023 Oct 30;15(1):187. doi: 10.1186/s13195-023-01337-z. Alzheimers Res Ther. 2023. PMID: 37899431 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical