Amyloid Plaques

1
?-Amyloid Plaques
SIGMA-ALDRICH
2
?-Amyloid Plaques Neurodegenerative diseases are
a varied assortment of central nervous system
disorders characterized by neuronal loss and
intraneuronal accumulations of fibrillary
materials. Abnormal protein-protein interactions
may allow the precipitation of these proteins,
forming intracellular and extracellular
aggregates. These abnormal interactions may play
a role in the dysfunction and death of neurons in
several common neurodegenerative diseases, such
as Alzheimers disease (AD) and Parkinsons
disease (PD). AD is characterized by loss of
function and death of nerve cells in the brain
leading to loss of cognitive function. The cause
of nerve cell death is unknown but fibrillar
?-amyloid senile plaques (SP) and intraneuronal
tau-rich neurofibrillary tangles (NFT) are seen.
SP form by the extracellular accumulation of
amyloid beta (A?) peptide into amyloid deposits,
with the A?42 form being most prominant.
Proteolytic enzymes ?-secretase and ?-secretase
sequentially cleave the ?-amyloid precursor
protein (APP) into A?. The enzyme BACE (?-site
APP cleaving enzyme) has been identified as
?-secretase. NFT are made up of aggregated
hyperphosphorylated tau protein. Abnormal
phosphorylation, possibly caused by mutations in
the tau gene, may be one of the events leading to
aggregation. References Walter, J., et al., The
cell biology of Alzheimer's disease uncovering
the secrets of secretases. Curr. Opin.
Neurobiol., 11, 585-590 (2001). Esler, W.P., and
Wolfe, M.S., A portrait of Alzheimer secretases -
new features and familiar faces. Science, 293,
1449-1454 (2001). Smith, M.A., et al., Amyloid-b,
tau alterations and mitochondrial dysfunction in
Alzheimer disease the chicken or the egg?
Neurochem. Int., 40, 527-531 (2002).