This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF

C Caudie

James R Connor

M Kawai

MW Brightman

O Carrette

RB Maccioni

ZB Redzic

English

PubMed

Crossref

Thompson EJ: Proteins of the Cerebrospinal Fluid. Elsevier Academic Press, New York.

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BioMed CentralCerebrospinal Fluid Research
ssOpen AcceBook review
Review of "Proteins of the Cerebrospinal Fluid" (2nd Edition) by 
Edward J. Thompson
James R Connor*
Address: Department of Neurosurgery, Pennsylvania State University, M.S. Hershey Medical Center, Hershey PA 17033, USA
Email: James R Connor* - jconnor@psu.edu
* Corresponding author    
Abstract
This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book
was written as an extension of a meeting on multiple sclerosis to provide a more extensive
consideration of the CSF.
Book details
Thompson EJ: 
Proteins of the Cerebrospinal Fluid.
  Elsevier Academic Press, New York.  ISBN: 0-12-369369-1 
Price: 135 (EUR) 149.95 (USD) Hardback; 332 pages
Review
My review of this book by Dr. Thompson is written in the
context of the reason I was drawn to this book and agreed
to read the book and provide a review. I was drawn to the
book based on its title because my research group was
about to make a significant commitment to proteomic
analyses of the cerebrospinal fluid (CSF) in both animal
models and human disease states. I expected that,
although I was familiar with CSF and the proteins that I
had been studying for many years, this book would pro-
vide a foundation and reference for me and the postdoc-
toral fellows and students in my laboratory as we
expanded our studies into the CSF. The forward indicated
that the book "makes for an encyclopedia type of book for
laboratory directors, experimentalists, etc". Therefore I
was looking for a book on proteomics of the CSF and per-
haps a state of the art assessment of protein profiling in
the CSF. The first chapter of the book, a historical perspec-
tive on CSF proteins, mentions mostly IgG and associated
methodologies. In Chapter 6 the discussion on pros and
cons of qualitative versus quantitative analysis, a key issue
in the evolving world of proteomics, is focused on IgG as
the "central issue' in the studies of CSF proteins. In addi-
tion, the options for quantitative approaches do not pro-
vide much information on the strengths of ELISAs or even
radioimmunoassays. The protocols are somewhat dated
but in a historical context; a reasonable resource. Thus,
this book is predominantly focused on immunoglobulins
in the CSF with a particular focus on the oligoclonal IgG
bands in multiple sclerosis. In the latter sense the book is
an excellent resource and outstanding review of the field
and the new investigator wishing to study immunoglobu-
lin in the CSF can benefit from the comments of the
author as a leader in this area from its beginning. As a
resource itself, the book has 1,322 references. The reader
interested in the broader topic of proteins in the CSF may
find this book does not meet expectations.
The book is divided into four segments. Part 1 has 5 chap-
ters and deals with normal CSF proteins in a "general fash-
ion". This section is a strength of the book and provides
useful background and organizational structure for the
new student of the CSF. The tables are particularly helpful,
providing information on the concentrations of different
proteins in the CSF relative to serum. There is a very good
reference table (4.4) on percentage transfer of proteins
Published: 26 January 2007
Cerebrospinal Fluid Research 2007, 4:1 doi:10.1186/1743-8454-4-1
Received: 29 November 2006
Accepted: 26 January 2007
This article is available from: http://www.cerebrospinalfluidresearch.com/content/4/1/1
© 2007 Connor; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
Cerebrospinal Fluid Research 2007, 4:1 http://www.cerebrospinalfluidresearch.com/content/4/1/1from serum to CSF. In contrast, many of the figures are
difficult to understand at best, and are overly simplistic.
For example, Figure 5.10 is a cartoon showing 6 sources of
CSF but the 6 sources are not labeled or otherwise identi-
fied in a figure legend.
In some of the functional discussions in this section there
are some questions about accuracy and some of the infor-
mation is dated. Despite the abundance of references for
this book, there are limited references in the discussion of
the different blood and CSF barriers that should be pro-
vided to support some of the statements that invoke data
as support. The function of prostaglandin synthase, induc-
tion of sleep when injected into the CSF, is confused with
its end product PDG2. In another example, there is a state-
ment that beta 2 microglobulin levels do not change in
neurological disorders. Although this statement appears
true for multiple sclerosis, there is certainly not uniform
agreement on this in other neurological disorders [1-3].
Later, in Chapter 11, there is a comment stating that the
ferritin synthesized within the brain is different from that
found within the serum, but this has never been sup-
ported beyond the single paper that the author cites.
Another example of limited consideration of important
topics is the rationale for why transferrin (Tf) without a
sialic acid moiety (tau) occurs in the CSF. The treatment
of this protein (and others) fails to consider the possibility
that Tf made in the choroid plexus [4] can be released into
the CSF and at one point refers to "presumed local synthe-
sis" of Tf in Chapter 7. The figure provided as an explana-
tion (Figure 5.7) for the presence of asialic Tf in the CSF is
overly simplistic.
Comments such as protein released into the CSF by
"white matter" may be carried down into the lumbar sac
but any that are released through the cerebral cortex are
swept into the arachnoid villi are difficult to understand
and lack evidence to support them. Another such puzzling
comment is that electron microscopists had previously
assumed that there was no interstitial space until more
recent techniques for tissue fixation were developed.
Although historically accurate, the existence of interstitial
space in the brain has been known for well over 30 years
(see reference [5] for review).
Part 2 is described by the author as dealing with normal
CSF proteins in a more specific fashion, but the chapters
only review immunoglobulins. The subjects discussed can
be, however, made applicable to other proteins. There is a
discussion in Chapter 7 on movement of drugs across the
BBB that will be appreciated by the novice investigator.
Chapter 8 develops mathematical models to evaluate the
source of IgG proteins in the CSF. Chapter 9 develops the
idea that the most biologically stable values for normal
barrier function are the ratios of IgG to albumin in CSF
and serum. The rationale behind this latter statement is
somewhat underdeveloped but does not appear to be
inaccurate. The major focus of the chapter is again on the
IgG levels. A number of points are introduced that could
be extremely useful such as the observation that there is a
circadian rhythm of the CSF, with a 6-fold increase in CSF
production at night. This information is important for
new investigators attempting to use CSF to obtain profiles
for disease biomarkers and could have been emphasized
more.
Part 3 is a "mini-clinical" book dealing with individual
diseases. Chapter 10 of this section is dedicated to IgG
production in the CSF, mostly in multiple sclerosis. The
author misses an opportunity to use his historical perspec-
tive and experience in CSF biology to address the develop-
ing field of proteomics and the search for biomarkers for
various diseases that reflect more than the degree of infec-
tion. In Chapter 11, the non-immunoglobulin proteins
are given too little consideration and there are some both-
ersome comments such as myelin basic protein is referred
to as the "best studied protein in the brain". Normal Pres-
sure hydrocephalus is mentioned in the context of two
proteins that appear enriched in the CSF of patients with
this disorder. Given the vantage point of the author in CSF
biology, this reader was left wanting for comments on the
potential for using CSF protein profiles to differentiate
NPH from Alzheimer's Disease. In context of the latter dis-
ease there is no mention of amyloid or A-beta fragments
that many laboratories are trying to identify in CSF as a
diagnostic indicator for AD [6]. The conclusion of Chapter
11 fails to mention proteomics when suggesting future
directions for the use of CSF as a diagnostic marker. Chap-
ter 13 is a reasonable review of the state of the field to use
CSF as a prognostic indicator with a good summary table.
In the chapter on future growth areas (Chapter 14) there
are 5 lines dedicated to proteomics.
Part 4 is a mini laboratory book with a series of appendi-
ces providing protocols for analysis of CSF proteins. The
protocols are standard gel analyses, but the author makes
comments from his vast experience that would be helpful
for those wishing to evaluate immunoglobulins in partic-
ular.
In summary, despite what I am sure appears to be a luke-
warm review, this is not a disappointing book and is a
good reference source for the new CSF investigator. The
title is misleading and, thus if the reader is looking for a
resource on CSF proteins and function, they will need to
continue to look beyond this book. At the end of Chapter
14 on future growth areas the author concludes that "in
the future, CSF is still not likely to be ignored". The author
definitely reaches the right conclusion, but did not takePage 2 of 3
(page number not for citation purposes)
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full advantage of the opportunity to use this book and his
considerable knowledge to serve as a guiding source for
the next generation of CSF investigations and investiga-
tors.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
Sole author
References
1. Caudie C, Bancel J, Dupont M, Matanza D, Poitevin F, Honnorat J:
[CSF levels and diagnostic utility of cerebrospinal fluid
beta2-microglobulin].  Ann Biol Clin (Paris) 2005, 63:631-637.
2. Carrette O, Demalte I, Scherl A, Yalkinoglu O, Corthals G, Burkhard
P, Hochstrasser DF, Sanchez JC: A panel of cerebrospinal fluid
potential biomarkers for the diagnosis of Alzheimer's dis-
ease.  Proteomics 2003, 3:1486-1494.
3. Kawai M, Hirohata S: Cerebrospinal fluid beta(2)-microglobulin
in neuro-Behcet's syndrome.  J Neurol Sci 2000, 179:132-139.
4. Redzic ZB, Segal MB: The structure of the choroid plexus and
the physiology of the choroid plexus epithelium.  Adv Drug Deliv
Rev 2004, 56:1695-1716.
5. Brightman MW, Kaya M: Permeable endothelium and the inter-
stitial space of brain.  Cell Mol Neurobiol 2000, 20:111-130.
6. Maccioni RB, Lavados M, Maccioni CB, Mendoza-Naranjo A: Biolog-
ical markers of Alzheimer's disease and mild cognitive
impairment.  Curr Alzheimer Res 2004, 1:307-314.Page 3 of 3
(page number not for citation purposes)


Abstract This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.</p

Connor James R

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Review of "Proteins of the Cerebrospinal Fluid" (2<sup>nd </sup>Edition) by Edward J. Thompson

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