Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly

Randall (Randy) Woltjer, Joshua A. Sonnen, Izabela Sokal, Lisa G. Rung, Wan Yang, John D. Kjerulf, Danielle Klingert, Charles Johnson, Isaac Rhew, Debbie Tsuang, Paul K. Crane, Eric B. Larson, Thomas J. Montine

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Accumulation of abnormal protein aggregates, detergent-insoluble (DI) proteins and amyloid in the brain are shared features of many neurodegenerative diseases. Previous studies correlating DI proteins and cognitive performance are limited. We addressed these limitations using two sets of autopsy brains, one selected from our Alzheimer's Disease Research Center and the other an unselected series from Adult Changes in Thought (ACT), a population-based study of brain aging. We observed concentrations of 11 proteins and 6 protein variants that can be grouped into three highly correlated clusters: amyloid (A)β, tau and alpha-synuclein (α-syn). While abnormal proteins from each cluster independently correlated with cognitive performance in ACT participants, only increased soluble Aβ oligomers in temporal cortex and increased DI Aβ 42 and DI α-syn in prefrontal cortex were negatively correlated with cognitive performance. These data underscore the therapeutic imperative to suppress processes leading to accumulation of soluble Aβ oligomers, DI Aβ 42 and DI α-syn, highlight an at least partially independent contribution to cognitive impairment and raise the possibility that the priority for therapeutic targets may vary by brain region in a typical elderly US population.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalBrain Pathology
Volume19
Issue number3
DOIs
StatePublished - Jul 2009

Fingerprint

Detergents
Proteins
Brain
Amyloidogenic Proteins
alpha-Synuclein
Temporal Lobe
Prefrontal Cortex
Amyloid
Neurodegenerative Diseases
Population
Autopsy
Alzheimer Disease
Therapeutics
Research

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Woltjer, R. R., Sonnen, J. A., Sokal, I., Rung, L. G., Yang, W., Kjerulf, J. D., ... Montine, T. J. (2009). Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly. Brain Pathology, 19(3), 365-374. https://doi.org/10.1111/j.1750-3639.2008.00190.x

Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly. / Woltjer, Randall (Randy); Sonnen, Joshua A.; Sokal, Izabela; Rung, Lisa G.; Yang, Wan; Kjerulf, John D.; Klingert, Danielle; Johnson, Charles; Rhew, Isaac; Tsuang, Debbie; Crane, Paul K.; Larson, Eric B.; Montine, Thomas J.

In: Brain Pathology, Vol. 19, No. 3, 07.2009, p. 365-374.

Research output: Contribution to journalArticle

Woltjer, RR, Sonnen, JA, Sokal, I, Rung, LG, Yang, W, Kjerulf, JD, Klingert, D, Johnson, C, Rhew, I, Tsuang, D, Crane, PK, Larson, EB & Montine, TJ 2009, 'Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly', Brain Pathology, vol. 19, no. 3, pp. 365-374. https://doi.org/10.1111/j.1750-3639.2008.00190.x
Woltjer, Randall (Randy) ; Sonnen, Joshua A. ; Sokal, Izabela ; Rung, Lisa G. ; Yang, Wan ; Kjerulf, John D. ; Klingert, Danielle ; Johnson, Charles ; Rhew, Isaac ; Tsuang, Debbie ; Crane, Paul K. ; Larson, Eric B. ; Montine, Thomas J. / Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly. In: Brain Pathology. 2009 ; Vol. 19, No. 3. pp. 365-374.
@article{d9a66fd96ac64c5e98a75d0e567f28c4,
title = "Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly",
abstract = "Accumulation of abnormal protein aggregates, detergent-insoluble (DI) proteins and amyloid in the brain are shared features of many neurodegenerative diseases. Previous studies correlating DI proteins and cognitive performance are limited. We addressed these limitations using two sets of autopsy brains, one selected from our Alzheimer's Disease Research Center and the other an unselected series from Adult Changes in Thought (ACT), a population-based study of brain aging. We observed concentrations of 11 proteins and 6 protein variants that can be grouped into three highly correlated clusters: amyloid (A)β, tau and alpha-synuclein (α-syn). While abnormal proteins from each cluster independently correlated with cognitive performance in ACT participants, only increased soluble Aβ oligomers in temporal cortex and increased DI Aβ 42 and DI α-syn in prefrontal cortex were negatively correlated with cognitive performance. These data underscore the therapeutic imperative to suppress processes leading to accumulation of soluble Aβ oligomers, DI Aβ 42 and DI α-syn, highlight an at least partially independent contribution to cognitive impairment and raise the possibility that the priority for therapeutic targets may vary by brain region in a typical elderly US population.",
author = "Woltjer, {Randall (Randy)} and Sonnen, {Joshua A.} and Izabela Sokal and Rung, {Lisa G.} and Wan Yang and Kjerulf, {John D.} and Danielle Klingert and Charles Johnson and Isaac Rhew and Debbie Tsuang and Crane, {Paul K.} and Larson, {Eric B.} and Montine, {Thomas J.}",
year = "2009",
month = "7",
doi = "10.1111/j.1750-3639.2008.00190.x",
language = "English (US)",
volume = "19",
pages = "365--374",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Quantitation and mapping of cerebral detergent-insoluble proteins in the elderly

AU - Woltjer, Randall (Randy)

AU - Sonnen, Joshua A.

AU - Sokal, Izabela

AU - Rung, Lisa G.

AU - Yang, Wan

AU - Kjerulf, John D.

AU - Klingert, Danielle

AU - Johnson, Charles

AU - Rhew, Isaac

AU - Tsuang, Debbie

AU - Crane, Paul K.

AU - Larson, Eric B.

AU - Montine, Thomas J.

PY - 2009/7

Y1 - 2009/7

N2 - Accumulation of abnormal protein aggregates, detergent-insoluble (DI) proteins and amyloid in the brain are shared features of many neurodegenerative diseases. Previous studies correlating DI proteins and cognitive performance are limited. We addressed these limitations using two sets of autopsy brains, one selected from our Alzheimer's Disease Research Center and the other an unselected series from Adult Changes in Thought (ACT), a population-based study of brain aging. We observed concentrations of 11 proteins and 6 protein variants that can be grouped into three highly correlated clusters: amyloid (A)β, tau and alpha-synuclein (α-syn). While abnormal proteins from each cluster independently correlated with cognitive performance in ACT participants, only increased soluble Aβ oligomers in temporal cortex and increased DI Aβ 42 and DI α-syn in prefrontal cortex were negatively correlated with cognitive performance. These data underscore the therapeutic imperative to suppress processes leading to accumulation of soluble Aβ oligomers, DI Aβ 42 and DI α-syn, highlight an at least partially independent contribution to cognitive impairment and raise the possibility that the priority for therapeutic targets may vary by brain region in a typical elderly US population.

AB - Accumulation of abnormal protein aggregates, detergent-insoluble (DI) proteins and amyloid in the brain are shared features of many neurodegenerative diseases. Previous studies correlating DI proteins and cognitive performance are limited. We addressed these limitations using two sets of autopsy brains, one selected from our Alzheimer's Disease Research Center and the other an unselected series from Adult Changes in Thought (ACT), a population-based study of brain aging. We observed concentrations of 11 proteins and 6 protein variants that can be grouped into three highly correlated clusters: amyloid (A)β, tau and alpha-synuclein (α-syn). While abnormal proteins from each cluster independently correlated with cognitive performance in ACT participants, only increased soluble Aβ oligomers in temporal cortex and increased DI Aβ 42 and DI α-syn in prefrontal cortex were negatively correlated with cognitive performance. These data underscore the therapeutic imperative to suppress processes leading to accumulation of soluble Aβ oligomers, DI Aβ 42 and DI α-syn, highlight an at least partially independent contribution to cognitive impairment and raise the possibility that the priority for therapeutic targets may vary by brain region in a typical elderly US population.

UR - http://www.scopus.com/inward/record.url?scp=66949127883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66949127883&partnerID=8YFLogxK

U2 - 10.1111/j.1750-3639.2008.00190.x

DO - 10.1111/j.1750-3639.2008.00190.x

M3 - Article

C2 - 18652590

AN - SCOPUS:66949127883

VL - 19

SP - 365

EP - 374

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 3

ER -