Fluctuations in Protein Aggregation: Design of Preclinical Screening for Early Diagnosis of Neurodegenerative Disease

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Fluctuations in Protein Aggregation : Design of Preclinical Screening for Early Diagnosis of Neurodegenerative Disease. / Costantini, Giulio; Budrikis, Zoe; Taloni, Alessandro; Buell, Alexander K.; Zapperi, Stefano; La Porta, Caterina A. M.

In: Physical Review Applied, Vol. 6, No. 3, 034012, 21.09.2016.

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Costantini, Giulio ; Budrikis, Zoe ; Taloni, Alessandro ; Buell, Alexander K. ; Zapperi, Stefano ; La Porta, Caterina A. M. / Fluctuations in Protein Aggregation : Design of Preclinical Screening for Early Diagnosis of Neurodegenerative Disease. In: Physical Review Applied. 2016 ; Vol. 6, No. 3.

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@article{44fba44a92c8445fb3691c19737161fd,
title = "Fluctuations in Protein Aggregation: Design of Preclinical Screening for Early Diagnosis of Neurodegenerative Disease",
abstract = "Autocatalytic fibril nucleation has recently been proposed to be a determining factor for the spread of neurodegenerative diseases, but the same process could also be exploited to amplify minute quantities of protein aggregates in a diagnostic context. Recent advances in microfluidic technology allow the analysis of protein aggregation in micron-scale samples, potentially enabling such diagnostic approaches, but the theoretical foundations for the analysis and interpretation of such data are, so far, lacking. Here, we study computationally the onset of protein aggregation in small volumes and show that the process is ruled by intrinsic fluctuations whose volume-dependent distribution we also estimate theoretically. Based on these results, we develop a strategy to quantify in silico the statistical errors associated with the detection of aggregate-containing samples. Our work explores a different perspective on the forecasting of protein aggregation in asymptomatic subjects.",
keywords = "ALPHA-SYNUCLEIN AGGREGATION, ALZHEIMERS-DISEASE, NUCLEATION, KINETICS, CHEMISTRY, MECHANISM, PEPTIDES, GROWTH, PHASE",
author = "Giulio Costantini and Zoe Budrikis and Alessandro Taloni and Buell, {Alexander K.} and Stefano Zapperi and {La Porta}, {Caterina A. M.}",
year = "2016",
month = "9",
day = "21",
doi = "10.1103/PhysRevApplied.6.034012",
language = "English",
volume = "6",
journal = "Physical Review Applied",
issn = "2331-7019",
publisher = "American Physical Society",
number = "3",

}

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TY - JOUR

T1 - Fluctuations in Protein Aggregation

T2 - Design of Preclinical Screening for Early Diagnosis of Neurodegenerative Disease

AU - Costantini, Giulio

AU - Budrikis, Zoe

AU - Taloni, Alessandro

AU - Buell, Alexander K.

AU - Zapperi, Stefano

AU - La Porta, Caterina A. M.

PY - 2016/9/21

Y1 - 2016/9/21

N2 - Autocatalytic fibril nucleation has recently been proposed to be a determining factor for the spread of neurodegenerative diseases, but the same process could also be exploited to amplify minute quantities of protein aggregates in a diagnostic context. Recent advances in microfluidic technology allow the analysis of protein aggregation in micron-scale samples, potentially enabling such diagnostic approaches, but the theoretical foundations for the analysis and interpretation of such data are, so far, lacking. Here, we study computationally the onset of protein aggregation in small volumes and show that the process is ruled by intrinsic fluctuations whose volume-dependent distribution we also estimate theoretically. Based on these results, we develop a strategy to quantify in silico the statistical errors associated with the detection of aggregate-containing samples. Our work explores a different perspective on the forecasting of protein aggregation in asymptomatic subjects.

AB - Autocatalytic fibril nucleation has recently been proposed to be a determining factor for the spread of neurodegenerative diseases, but the same process could also be exploited to amplify minute quantities of protein aggregates in a diagnostic context. Recent advances in microfluidic technology allow the analysis of protein aggregation in micron-scale samples, potentially enabling such diagnostic approaches, but the theoretical foundations for the analysis and interpretation of such data are, so far, lacking. Here, we study computationally the onset of protein aggregation in small volumes and show that the process is ruled by intrinsic fluctuations whose volume-dependent distribution we also estimate theoretically. Based on these results, we develop a strategy to quantify in silico the statistical errors associated with the detection of aggregate-containing samples. Our work explores a different perspective on the forecasting of protein aggregation in asymptomatic subjects.

KW - ALPHA-SYNUCLEIN AGGREGATION

KW - ALZHEIMERS-DISEASE

KW - NUCLEATION

KW - KINETICS

KW - CHEMISTRY

KW - MECHANISM

KW - PEPTIDES

KW - GROWTH

KW - PHASE

U2 - 10.1103/PhysRevApplied.6.034012

DO - 10.1103/PhysRevApplied.6.034012

M3 - Article

VL - 6

JO - Physical Review Applied

JF - Physical Review Applied

SN - 2331-7019

IS - 3

M1 - 034012

ER -

ID: 9026170