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Volume 17, Number 24,
Issue of December 15, 1997
pp. 9407-9414
The  -Amyloid Precursor Protein of Alzheimer's Disease
Enhances Neuron Viability and Modulates Neuronal Polarity
Received July 24, 1997; revised Sept. 2, 1997; accepted Sept. 24, 1997.
Ruth G. Perez1, 3,
Hui Zheng4,
Lex H. T. Van der
Ploeg4, and
Edward H. Koo2, 3
Departments of 1 Neurology and 2 Pathology,
Harvard Medical School, Boston, Massachusetts 02115, 3 Center for Neurological Diseases, Brigham and Women's
Hospital, Boston, Massachusetts 02115, and 4 Department of
Genetics and Molecular Biology, Merck Research Laboratories, Rahway,
New Jersey 07065
 -Amyloid precursor protein (PP) can reside at neuron and
glial cell surfaces or undergo proteolytic processing into secreted fragments. Although PP has been studied extensively, its precise physiological role is unknown. A line of transgenic knock-out mice
selectively deficient in PP survive and breed but exhibit motor
dysfunction and brain gliosis, consistent with a physiological role for
PP in neuron development. To elucidate these functions, we cultured
hippocampal neurons from wild-type and PP-deficient mice and
compared their ability to attach, survive, and develop neurites. We
found that hippocampal neurons from PP-deficient mice had diminished
viability and retarded neurite development. We also compared the
effects of PP secretory products, released from wild-type
astrocytes, on process outgrowth from wild-type and PP-deficient
hippocampal neurons. Outgrowth was enhanced at 1 d in the presence
of wild-type astrocytes, as compared with PP-deficient astrocytes.
However, by 3 d, neurons had shorter axons but more minor
processes with more branching when cocultured with wild-type
astrocytes, as compared with PP-deficient astrocytes. Our data
demonstrate that cell-associated neuronal PP contributes to neuron
viability, axonogenesis, and arborization and that PP secretory
products modulate axon growth, dendrite branching, and dendrite
numbers.
Key words:
arborization;
astrocytes;
axonogenesis;
A;
PP;
PPs;
knock-out mice;
neurite outgrowth;
neuron
survival
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|
|
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|
|
|
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|
|
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[Full Text]
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|
|
|
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142(1):
191 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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|
|
|
|
|
|
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J. Biol. Chem.,
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276(36):
33923 - 33929.
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|
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