Key Factors in Alzheimer's Disease: β‐amyloid Precursor Protein Processing, Metabolism and Intraneuronal Transport
- 1 January 2001
- journal article
- review article
- Published by Wiley in Brain Pathology
- Vol. 11 (1) , 1-11
- https://doi.org/10.1111/j.1750-3639.2001.tb00376.x
Abstract
During the last years it has become evident that the β‐amyloid (Aβ) component of senile plaques may be the key molecule in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Aβ, however, is still a matter of controversy. The precursor of the β‐amyloid peptide is the predominantly neuronal β‐amyloid precursor protein. We, and others, hypothesize that intraneuronal misregulation of APP leads to an accumulation of Aβ peptides in intracellular compartments. This accumulation impairs APP trafficking, which starts a cascade of pathological changes and causes the pyramidal neurons to degenerate. Enhanced Aβ secretion as a function of stressed neurons and remnants of degenerated neurons provide seeds for extracellular Aβ aggregates, which induce secondary degenerative events involving neighboring cells such as neurons, astroglia and macrophages/microglia.Keywords
This publication has 91 references indexed in Scilit:
- Intracellular Accumulation of Insoluble, Newly Synthesized Aβn-42 in Amyloid Precursor Protein-transfected Cells That Have Been Treated with Aβ1–42Journal of Biological Chemistry, 1999
- The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signalingProgress in Neurobiology, 1998
- Presenilin 1 Regulates the Processing of β-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid β-Protein in Endoplasmic Reticulum and GolgiBiochemistry, 1998
- The X11α Protein Slows Cellular Amyloid Precursor Protein Processing and Reduces Aβ40 and Aβ42 SecretionJournal of Biological Chemistry, 1998
- The Role of APP Processing and Trafficking Pathways in the Formation of Amyloid β‐ProteinaAnnals of the New York Academy of Sciences, 1996
- Intracellular routing of human amyloid protein precursor: Axonal delivery followed by transport to the dendritesJournal of Neuroscience Research, 1995
- APP gene family: unique age-associated changes in splicing of Alzheimer's βA4-amyloid protein precursorNeurobiology of Disease, 1994
- Alzheimer's Disease Families with Amyloid Precursor Protein MutationsaAnnals of the New York Academy of Sciences, 1993
- Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway.The Journal of cell biology, 1993
- Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid proteinBiochemical and Biophysical Research Communications, 1984