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From: TSS ()
Subject: Re: Alzheimer’s may 'seed' itself like mad cow disease
Date: September 21, 2006 at 1:22 pm PST

In Reply to: Alzheimer’s may 'seed' itself like mad cow disease posted by TSS on September 21, 2006 at 11:46 am:


Exogenous Induction of Cerebral

b-Amyloidogenesis Is Governed

by Agent and Host

Melanie Meyer-Luehmann,1* Janaky Coomaraswamy,1* Tristan Bolmont,1,2* Stephan Kaeser,1

Claudia Schaefer,1 Ellen Kilger,1 Anton Neuenschwander,3 Dorothee Abramowski,3 Peter Frey,3

Anneliese L. Jaton,3 Jean-Marie Vigouret,3 Paolo Paganetti,3 Dominic M. Walsh,4

Paul M. Mathews,5 Jorge Ghiso,6 Matthias Staufenbiel,3 Lary C. Walker,7† Mathias Jucker1,2†

Protein aggregation is an established pathogenic mechanism in Alzheimer’s disease, but little is

known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-b (Ab)–

containing brain extracts from humans with Alzheimer’s disease or b-amyloid precursor protein

(APP) transgenic mice induced cerebral b-amyloidosis and associated pathology in APP transgenic

mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was

reduced or abolished by Ab immunodepletion, protein denaturation, or by Ab immunization of the

host. The phenotype of the exogenously induced amyloidosis depended on both the host and the

source of the agent, suggesting the existence of polymorphic Ab strains with varying biological

activities reminiscent of prion strains.

snip...

There is currently no evidence that bamyloidosis

(and in particular AD) is transmissible

in the same sense as are prion diseases,

which can be transmitted to wild-type hosts via

diverse routes of varying efficiency and involve

systemic cellular mechanisms of prion uptake

and distribution (7, 32). However, an understanding

of the mechanisms involved in the

instigation and propagation of abnormal Ab

assemblies in vivo could shed light on the

origins of idiopathic Alzheimer_s disease. .............END

http://www.sciencemag.org/cgi/content/abstract/313/5794/1781

tss



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