February 24, 2003

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Extracellular amyloid

b-amyloid in the extracellular space
spreads Alzheimer's pathology. | By Tudor
P Toma

Alzheimer's disease (AD) is a
neurodegenerative disorder characterized
by aggregation of b-amyloid peptide (Ab)
into senile plaques and cerebrovascular
amyloid. It remains unclear if amyloid is
initiated by the accumulation of Ab in the
extracellular space or by intraneuronal Ab
generation. In February 24 advanced
online Nature Neuroscience, Melanie
Meyer-Luehmann and colleagues at the
University of Basel, Switzerland, show
that diffusion of soluble Ab in the
extracellular space is involved in the
spread of Ab pathology, and that
extracellular amyloid formation can lead
to neurodegeneration (Nature
Neuroscience, DOI:10.1038/nn1022,
February 24, 2003).

Meyer-Luehmann et al. used APP23
transgenic (Tg) mice that develop
cerebral amyloid with aging. After
transplanting wild-type (WT) and APP23
embryonic brain tissue into the brains of
both Tg and WT mice, they observed that
APP23 grafts into wild-type hosts did not
develop amyloid deposits for up to 20
months following grafting. In contrast,
both transgenic and wild-type grafts into
APP hosts developed amyloid plaques as
early as 3 months after grafting. In
addition, they showed that the amyloid
deposits in wild-type grafts were
surrounded by neuritic changes and
gliosis, similar to the amyloid-associated
pathology described in APP23 mice.

"Overall, our findings show that factors
beyond those directly involved in cellular
Ab production and intracellular Ab
metabolism are important for
amyloidogenesis in vivo. The amyloid
associated pathology in WT grafts further
suggests that neurodegeneration in AD is
dependent, at least partially, upon
extracellular amyloid accumulation,"
conclude the authors.
Links for this article
J. Hardy et al., "The amyloid hypothesis of
Alzheimer's disease: progress and
problems on the road to therapeutics,"
Science, 297:353-356, 2002.
[PubMed Abstract]  
M. Meyer-Luehmann et al., "Extracellular
amyloid formation and associated
pathology in neural grafts," Nature
Neuroscience, DOI:10.1038/nn1022,
February 24, 2003.
http://www.nature.com/natureneuroscienc
e 
University of Basel
http://www.unibas.ch/ 
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