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Cell Rep. 2014 Apr 10;7(1):261-8. doi: 10.1016/j.celrep.2014.02.031. Epub 2014 Mar 20.

Detection of misfoldedoligomers for sensitive biochemical diagnosis of Alzheimer's disease.

Author information

1
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
2
Neurology Unit, Università di Milano, Centro Dino Ferrari, Fondazione Ca' Granda, IRCC Ospedale Policlinico, via F. Sforza 35, 20122 Milan, Italy.
3
IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
4
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: claudio.soto@uth.tmc.edu.

Abstract

Alzheimer's disease (AD) diagnosis is hampered by the lack of early, sensitive, and objective laboratory tests. We describe a sensitive method for biochemical diagnosis of AD based on specific detection of misfoldedoligomers, which play a central role in AD pathogenesis. The protein misfolding cyclic amplification assay (Aβ-PMCA), exploits the functional property of Aβ oligomers to seed the polymerization of monomeric Aβ. Aβ-PMCA allowed detection of as little as 3 fmol of Aβ oligomers. Most importantly, using cerebrospinal fluid, we were able to distinguish AD patients from control individuals affected by a variety of other neurodegenerative disorders or nondegenerative neurological diseases with overall sensitivity of 90% and specificity of 92%. These findings provide the proof-of-principle basis for developing a highly sensitive and specific biochemical test for AD diagnosis.

PMID:
24656814
DOI:
10.1016/j.celrep.2014.02.031
[Indexed for MEDLINE]
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