You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


Advertisement

ABOUT ARCHIVES
Advanced Search

Welcome   | My Account | E-mail Alerts | RSS | Access Rights | Sign In


  Vol. 65 No. 7, July 2008 TABLE OF CONTENTS
  Online Only
 •  Online First Table of
Contents
  Original Contribution
 •Online Features
 This Article
 •Full text
 •PDF
 • Reply to article
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on HighWire
 •Citing articles on Web of Science (24)
 •Contact me when this article is cited
 Related Content
 •Related articles
 •Similar articles in this journal
 Topic Collections
 •Neurology
 •Alzheimer Disease
 •Cognitive Disorders
 •Neurogenetics
 •Neurology, Other
 •Genetic Disorders
 •Genetics, Other
 •Alert me on articles by topic
 Social Bookmarking
  Add to CiteULike Add to Connotea Add to Delicious Add to Digg Add to Facebook Add to Reddit Add to Technorati Add to Twitter What's this?

Distinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain

A Clinicopathologic Study

Joshua R. Steinerman, MD; Michael Irizarry, MD; Nikolaos Scarmeas, MD; Susan Raju, PhD; Jason Brandt, PhD; Marilyn Albert, PhD; Deborah Blacker, MD; Bradley Hyman, MD, PhD; Yaakov Stern, PhD

Arch Neurol. 2008;65(7):906-912.

Objective  To determine whether β-amyloid (Aβ) peptides segregated into distinct biochemical compartments would differentially correlate with clinical severity of Alzheimer disease (AD).

Design  Clinicopathologic correlation study.

Participants  Twenty-seven patients from a longitudinal study of AD and 13 age- and sex-matched controls without a known history of cognitive impairment or dementia were included in this study.

Interventions  Temporal and cingulate neocortex were processed using a 4-step extraction, yielding biochemical fractions that are hypothesized to be enriched with proteins from distinct anatomical compartments: TRIS (extracellular soluble), Triton (intracellular soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid (extracellular insoluble). Levels of Aβ40 and Aβ42 were quantified in each biochemical compartment by enzyme-linked immunosorbent assay.

Results  The Aβ42 level in all biochemical compartments was significantly elevated in patients with AD vs controls (P < .01). The Aβ40 levels in the TRIS and formic acid fractions were elevated in patients with AD (temporal, P < .01; cingulate, P = .03); however, Triton and SDS Aβ40 levels were similar in patients with AD and in controls. Functional impairment proximal to death correlated with Triton Aβ42 (r = 0.48, P = .02) and SDS Aβ42 (r = 0.41, P = .04) in the temporal cortex. Faster cognitive decline was associated with elevated temporal SDS Aβ42 levels (P < .001), whereas slower decline was associated with elevated cingulate formic acid Aβ42 and SDS Aβ42 levels (P = .02 and P = .01, respectively).

Conclusion  Intracellular and membrane-associated Aβ, especially Aβ42 in the temporal neocortex, may be more closely related to AD symptoms than other measured Aβ species.


Author Affiliations: Departments of Neurology (Drs Steinerman and Scarmeas), Psychiatry (Dr Stern), and Psychology (Dr Stern), Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York; Departments of Neurology (Drs Irizarry, Raju, and Hyman) and Psychiatry (Dr Blacker), Massachusetts General Hospital, Charlestown; and Departments of Psychiatry and Behavioral Sciences (Dr Brandt) and Neurology (Dr Albert), Johns Hopkins School of Medicine, Baltimore, Maryland. Dr Irizarry is now with GlaxoSmithKline, Research Triangle Park, NC.



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Delicious Delicious   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter     What's this?

RELATED ARTICLES

This Month in Archives of Neurology
Arch Neurol. 2008;65(7):871-872.
FULL TEXT  

Abeta Predictor of Alzheimer Disease Symptoms
Chantelle F. Sephton and Gang Yu
Arch Neurol. 2008;65(7):875-876.
EXTRACT | FULL TEXT  


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Neuronal Death Induced by Nanomolar Amyloid {beta} Is Mediated by Primary Phagocytosis of Neurons by Microglia
Neniskyte et al.
J. Biol. Chem. 2011;286:39904-39913.
ABSTRACT | FULL TEXT  

Suppression of a Neocortical Potassium Channel Activity by Intracellular Amyloid-{beta} and Its Rescue with Homer1a
Yamamoto et al.
J. Neurosci. 2011;31:11100-11109.
ABSTRACT | FULL TEXT  

CC Chemokine Receptor 2 Deficiency Aggravates Cognitive Impairments and Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
Naert and Rivest
J. Neurosci. 2011;31:6208-6220.
ABSTRACT | FULL TEXT  

The presence of sodium dodecyl sulphate-stable A{beta} dimers is strongly associated with Alzheimer-type dementia
Mc Donald et al.
Brain 2010;133:1328-1341.
ABSTRACT | FULL TEXT  

Synaptic transmission block by presynaptic injection of oligomeric amyloid beta
Moreno et al.
Proc. Natl. Acad. Sci. USA 2009;106:5901-5906.
ABSTRACT | FULL TEXT  

Abeta Predictor of Alzheimer Disease Symptoms
Sephton and Yu
Arch Neurol 2008;65:875-876.
FULL TEXT  





HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | PHYSICIAN JOBS | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 2008 American Medical Association. All Rights Reserved.