» Articles » PMID: 9566620

The Role of the Amyloid Protein Precursor (APP) in Alzheimer's Disease: Does the Normal Function of APP Explain the Topography of Neurodegeneration?

Overview
Journal Neurochem Res
Specialties Chemistry
Neurology
Date 1998 May 5
PMID 9566620
Citations 5
Authors
Affiliations
Soon will be listed here.
Abstract

Alzheimer's disease (AD) is the most common form of dementia in the aged population. Early-onset familial AD (FAD) involves mutations in a gene on chromosome 21 encoding the amyloid protein precursor or on chromosomes 14 or 1 encoding genes known as presenilins. All mutations examined have been found to increase the production of amyloidogenic forms of the amyloid protein (A beta), a 4 kDa peptide derived from APP. Despite the remarkable progress in elucidating the biochemical mechanisms responsible for AD, little is known about the normal function of APP. A model of how APP and A beta are involved in pathogenesis is presented. This model may explain why certain neuronal populations are selectively vulnerable in AD. It is suggested that those neurons which more readily undergo neuritic sprouting and synaptic remodelling are more vulnerable to A beta neurotoxicity.

Citing Articles

Proteasome activity modulates amyloid toxicity.

Galvin J, Curran E, Arteaga F, Goossens A, Aubuchon-Endsley N, McMurray M FEMS Yeast Res. 2022; 22(1).

PMID: 35150241 PMC: 8906389. DOI: 10.1093/femsyr/foac004.


Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells.

Mansor N, Ntimi C, Abdul-Aziz N, Ling K, Adam A, Rosli R Bosn J Basic Med Sci. 2020; 21(1):98-110.

PMID: 32156249 PMC: 7861624. DOI: 10.17305/bjbms.2020.4639.


Aberrant activation of focal adhesion proteins mediates fibrillar amyloid beta-induced neuronal dystrophy.

Grace E, Busciglio J J Neurosci. 2003; 23(2):493-502.

PMID: 12533609 PMC: 6741895.


Key factors in Alzheimer's disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport.

Bayer T, Wirths O, Majtenyi K, Hartmann T, Multhaup G, Beyreuther K Brain Pathol. 2001; 11(1):1-11.

PMID: 11145195 PMC: 8098450. DOI: 10.1111/j.1750-3639.2001.tb00376.x.


The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction.

Torroja L, Packard M, GORCZYCA M, White K, Budnik V J Neurosci. 1999; 19(18):7793-803.

PMID: 10479682 PMC: 6782486.

References
1.
Braak H, Braak E . Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol. 1996; 92(2):197-201. DOI: 10.1007/s004010050508. View

2.
Chartier-Harlin M, Crawford F, Houlden H, Warren A, Hughes D, Fidani L . Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature. 1991; 353(6347):844-6. DOI: 10.1038/353844a0. View

3.
Golde T, Estus S, Younkin L, Selkoe D, Younkin S . Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science. 1992; 255(5045):728-30. DOI: 10.1126/science.1738847. View

4.
Mann D, YATES P, Marcyniuk B, Ravindra C . The topography of plaques and tangles in Down's syndrome patients of different ages. Neuropathol Appl Neurobiol. 1986; 12(5):447-57. DOI: 10.1111/j.1365-2990.1986.tb00053.x. View

5.
Ninomiya H, Roch J, Jin L, Saitoh T . Secreted form of amyloid beta/A4 protein precursor (APP) binds to two distinct APP binding sites on rat B103 neuron-like cells through two different domains, but only one site is involved in neuritotropic activity. J Neurochem. 1994; 63(2):495-500. DOI: 10.1046/j.1471-4159.1994.63020495.x. View