Biomedical Engineering Reference
In-Depth Information
(a) A
b
(40)
(b) A
b
(42)
London APP Mice
London APP Mice
125
125
100
100
***
***
***
***
75
75
50
50
25
25
0
0
Control
CA074Me
E64d
Control
CA074Me
E64d
(c) CTF
b
(d) APP products: A
b
peptides and CTF
b
London APP Mice
150
ß-Secretase
APP
125
Aß
100
***
***
Secretase
75
CTFß, C-terminal fragment
Generated by ß-secretase
Aß
50
25
0
A
b
(40) and A
b
(42)
peptides
Control
CA074Me
E64d
Aß
Figure 6.8
The inhibitors CA074Me or E64d reduce brain Ab peptides and CTFb
derived from APP by WT b-secretase processing in London APP mice. (a)
Reduction in brain Ab40 after treatment of London AD mice with
CA074Me or E64d. London APP mice were treated with CA074Me or
E64d, and Ab40 levels in brain were measured by ELISA assays and
expressed as a percentage of the control Ab40 levels. Results are expressed
as the mean (% control)
SD, with statistical significance indicated
(***p
o
0.0001, Student's t-test). Brain levels of Ab40 are substantially
reduced after treatment with the inhibitors.
42
(b) Reduction in brain Ab42
after treatment of London AD mice with the inhibitors. After treatment of
London APP mice with CA074Me or E64d, Ab42 levels in brain were
measured by ELISA assays and expressed as a percentage of the control
Ab42. Results are expressed as the mean (% control)
SD, with statis-
tical significance indicated (***p
o
0.0001, Student's t-test). Brain levels of
Ab42 are decreased after treatment with the inhibitors.
42
(c) Reduced
CTFb in brain after inhibitor treatment. Analyses of CTFb derived from
APP by b-secretase in London APP mouse brains were performed with
brain extracts, and the CTFb band (12 kDa) was quantitated by densi-
tometry. Results show a decrease in CTFb after inhibitor treatment.
42
Results are expressed as the mean (% control)
SD, with statistical
significance indicated (***p
o
0.0001, Student's t-test). (d) Proteolytic
processing of APP into CTFb and Ab peptides by b- and g-secretases.
Cleavage of APP at the b-secretase site generates the C-terminal
b-secretase fragment (CTFb). Processing of CTFb by g-secretase results in
the generation of Ab peptides.
