Adhesion Molecules in Dementia - Adhesion Molecules - page 482

which is expressed by endothelial cells, platelets, and various leukocytes.
PECAM-1 is also a major constituent of the endothelial cell intercellular junction,
which is capable of mediating homophilic as well as heterophilic interactions. A
soluble form of VCAM-1 as well as PECAM have been identii ed in AD, but their
biological signii cance remains to be elucidated.
h e question whether circulating levels of various adhesion molecules are
associated with a risk for dementia remains to be answered. For instance, h e
Rotterdam Study has shown that levels of the soluble forms of ICAM-1 and
VCAM-1 are not associated with dementia risk (Engelhart et al . 2004). However,
from recent studies it appears that cognitively intact elderly subjects with CSF
levels of sICAM-1 above the median (> 893 ng/L) have a regional cerebral
blood l ow pattern similar to that seen in AD patients, i.e., increased frontal and
fronto-temporal and reduced temporo-parietal region l ow (Janciauskiene 2008).
Moreover, a signii cant correlation was found between CSF levels of sCD40 and
poor cognitive performance in elderly controls without cognitive symptoms
(Buchhave et al . 2009). Together, these i ndings indicate that some soluble adhesion
molecules may be elevated in the very early stages of preclinical AD.
THE INTEGRIN SUPERFAMILY MEMBERS IN DEMENTIA
Integrins constitute a superfamily of membrane proteins that allow individual
cells to communicate with their environment. h rough their interactions with
the extracellular matrix, external stimuli are transmitted internally through
the activation of various signaling cascades, thus allowing cells to adapt to
environmental changes. Integrins are expressed in all cells throughout the brain
and inl uence long-term potentiation (LTP) in hippocampal neurons, regulate
neurite outgrowth induced by growth factors, and regulate survival and death
signals. Integrins are expressed widely at dendritic spines and synapses in the
brain and are known to be involved in the regulation of synaptic transmission and
synaptic plasticity (Table 2) .
Consistent with this, synaptic plasticity was found to be strongly reduced
in Drosophila mutants in which a gene encoding synaptic integrins is deleted
(Rohrbough et al . 2000). Moreover, peptides containing the arginine-glycine-
aspartate (RGD) binding sequence, which is recognized by a large number of
integrins present in neurons, have been found to cause an inhibition of LTP (Bahr
et al . 1997) and mutant mice lacking integrin-associated protein, which is associated
with integrin and functions as a cell adhesion molecule, are also dei cient in LTP
(Chang et al . 1999). h ere is also an alteration of synaptic plasticity in mutant mice
lacking laminin α2, a glycoprotein abundant in basement membrane (Anderson
et al . 2005).