Ageing
Research
Reviews
11 (2012) 189–
198
Contents
lists
available
at
SciVerse
ScienceDirect
Ageing
Research
Reviews
j
ourna
l
ho
mepage:
www.elsevier.com/locate/arr
Review
Pentraxins
and
Alzheimer’s
disease:
At
the
interface
between
biomarkers
and
pharmacological
targets
Cecilia
Osera
a
,
Alessia
Pascale
a
,
Marialaura
Amadio
a
,
Letizia
Venturini
b,c
,
Stefano
Govoni
a
,
Giovanni
Ricevuti
b,c,∗
a
Department
of
Drug
Sciences,
Section
of
Pharmacology,
Laboratory
of
Neurobiology
and
Neuropharmacology
of
Neurodegenerative
Diseases
and
the
Nervous
System,
University
of
Pavia,
Viale
Taramelli
14,
27100
Pavia,
Italy
b
Laboratory
of
Cellular
Pathophysiology
and
Clinical
Immunology,
Fondazione
IRCCS
Policlinico
San
Matteo
Hospital,
Viale
Golgi
19,
27100
Pavia,
Italy
c
Department
of
Internal
Medicine
and
Therapeutics,
Section
of
Gerontology
and
Geriatrics
–
Alzheimer
Evaluation
Unit
–
IDR
S.
Margherita,
University
of
Pavia,
Via
Emilia
12,
27100
Pavia,
Italy
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
23
September
2011
Received
in
revised
form
21
November
2011
Accepted
6
December
2011
Available online 15 December 2011
Keywords:
Alzheimer’s
disease
Pentraxins
Neurodegeneration
Neuroinflammation
Microglia
a
b
s
t
r
a
c
t
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
involving
deposition
of
misfolded
proteins
in
vulnerable
brain
regions
leading
to
inexorable
and
progressive
neuronal
loss
and
deterioration
of
cogni-
tive
functions.
The
AD
brain
displays
features
typical
of
chronic
inflammation
as
defined
by
the
presence
of
activated
microglia
and
by
an
excessive
amount
of
neuroinflammatory
components
such
as
cytokines
and
acute-phase
proteins.
This
review
aims
to
shed
light
on
the
role
of
the
immune
processes
involved
in
AD,
focusing
on
a
family
of
inflammatory
modulators
belonging
to
the
acute-phase
proteins
and
crucial
components
of
the
humoral
arm
of
innate
immunity:
pentraxins.
In
particular
we
analyze
function
of
the
pentraxins
in
AD,
their
upregulation
in
the
brain
and
their
contribution
to
neurodegeneration.
Addition-
ally,
we
highlight
the
role
of
pentraxins
as
putative
AD
biomarkers
and
as
pharmacological
therapeutic
targets.
© 2011 Elsevier B.V. All rights reserved.
1.
Introduction
Since
the
1990s,
growing
evidence
has
pointed
to
the
contribu-
tion
of
inflammatory
and
immune
responses
to
neurodegeneration
(Akiyama
et
al.,
2000).
The
mammalian
immune
system
is
a
well-orchestrated
signaling
network
involving
both
innate
and
adaptive
immunity.
Innate
immunity,
consisting
of
both
cellular
and
humoral
arms
protects
the
host
against
invading
organ-
isms,
plays
an
important
role
in
activating
adaptive
immunity
and
in
maintaining
tissue
integrity
and
repair.
The
humoral
arm
includes
the
phylogenetically
conserved
multifunctional
pentraxin
superfamily,
whose
components,
acting
as
acute
phase
proteins,
represent
the
functional
ancestors
of
antibodies
(Bottazzi
et
al.,
2010).
Pentraxins
are
characterized
by
a
cyclic
multimeric
struc-
ture
whose
carboxy-terminal
contains
a
conserved
eight
aminoacid
∗
Corresponding
author
at:
Laboratory
of
Cellular
Pathophysiology
and
Clinical
Immunology,
Fondazione
IRCCS
Policlinico
San
Matteo
Hospital,
Viale
Golgi
19,
27100
Pavia,
Italy.
Tel.:
+39
0382381233;
fax:
+39
0382465447.
E-mail
addresses:
cecilia.osera@unipv.it
(C.
Osera),
alessia.pascale@unipv.it
(A.
Pascale),
marialaura.amadio@unipv.it
(M.
Amadio),
letizia.venturini@unipv.it
(L.
Venturini),
stefano.govoni@unipv.it
(S.
Govoni),
giovanni.ricevuti@unipv.it
(G.
Ricevuti).
sequence
known
as
the
“pentraxin
signature”
(Garlanda
et
al.,
2009).
According
to
the
primary
structure
of
the
protomer,
pen-
traxins
are
divided
into
short
and
long
pentraxins
(Garlanda
et
al.,
2005).
2.
The
pentraxin
family:
members
and
functions
2.1.
Short
pentraxins
The
most
studied
members
of
the
short
pentraxins
(Fig.
1)
are
glycoprotein
serum
amyloid
P
(SAP)
and
C-reactive
protein
(CRP)
which
in
humans
share
more
than
50%
aminoacid
homology
(Deban
et
al.,
2011).
Exclusively
produced
by
hepatocytes,
SAP
has
also
been
detected
in
cerebrospinal
fluid
(CSF)
and
in
the
brain
in
associa-
tion
with
amyloid
plaques
and
neurofibrillary
tangles,
key
features
of
Alzheimer’s
disease
(AD)
(Duong
et
al.,
1989;
Tennent
et
al.,
1995).
In
general,
SAP
is
considered
a
non-specific
marker
of
infec-
tion
and
inflammation,
as
its
serum
levels
remarkably
increase
following
IL-6-mediated
inflammatory
response.
Like
SAP,
CRP
is
used
as
a
general
diagnostic
marker
of
inflammation
mediated
by
IL-6
and
IL-1
activation
(Steel
and
Whitehead,
1994;
Macy
et
al.,
1997).
Mainly
produced
by
hepatocytes,
CRP,
like
SAP,
has
been
1568-1637/$
–
see
front
matter ©
2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.arr.2011.12.004