The
presenilin-1 (PS-1) gene was found on chromosome 14 and is responsible for
an early onset form of Alzheimer's disease (AD) that accounts for 70-80%
of the inherited forms of Alzheimer's. It is a membrane protein that has a
region where at least seven mutations have been identified in family
members with AD. The gene
sequence of PS-1 does not match any known human gene sequences with the
exception of PS-2; but has been found to be a new class of aspartic–proteases.
It has now been identified as one of the g-secretase
proteases.
Alzheimer’s disease (AD) is characterized by the
progressive formation in the brain of insoluble amyloid plaques and
vascular deposits consisting of the 4-kD amyloid b-peptide (Ab).
Ab
generation is initiated by proteolytic cleavage of the amyloid precursor
protein (APP) at the N-terminal of A$ by $-secretase (BACE).
The A$ peptide is then released by proteolytic cleavage at
its C-terminus by g-secretase (presenilins). Because both these proteases are prime candidates for
therapeutic intervention, an intense search has been underway to identify
these two enzymes.
A
goat antiserum to a synthetic peptide that corresponds to amino acids
14-33 of the N-terminus of the human PS-1 protein is currently available.
This antiserum has been shown to be immunoreactive with the unconjugated
immunizing peptide by ELISA, but does not show immunoreactivity with the
peptide used for the PS-2 antibody. This antiserum immunolabels neurons
using formalin-fixed, paraffin-embedded tissue sections. Western blot
analysis shows that the antibody immunolabels the intact 48 kD PS-1
protein, as well as the N-terminal fragment of the cleaved from of PS-1
that occurs in brain. This antibody should be a valuable tool for
scientists working to understand the role of PS-1 in Alzheimer’s
disease.
This
antiserum was produced using proprietary methodology whereby the peptide
is attached to a carrier that elicits minimal immunoreactivity so that the
antiserum has a higher degree of specificity for the peptide.
Since there is no overwhelming production of interfering antibodies
to the carrier, this antiserum can routinely be used without further
purification. Pseud-Immune™ control
immune serum (Cat no. GPA018E) from a mock immunized animal is available
to be used in conjunction with this antibody as well as the immunizing
peptide (Cat no. HSP006N), which can be used to neutralize
immunoreactivity
Manufacturing
Reference:
Southwest Immunology,
Inc., unpublished results.