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Aging-Related Memory Disorders
Alzheimer’s Disease
From Mechanisms of Memory by J. David Sweatt, Ph.D.
Amyloid Plaques and Neurofibrillary Tangles
Image by Poul Jorgensen, Claus Bus, Niels Pallisgaard, Marianne Bryder, and Arne Lund Jorgensen
A
B
C Terminus
N Terminus
Crystal Structure of Amyloid Beta Peptide
Watson et al (1998) Biochemistry 37:12700-12706.
Amyloid Precursor Protein (APP)
Price, Sisodia and Borchelt (1998) Science 282:1079-1083.
Tg 2576 Tg 2576 +PS1 A246E
PS1 A246E FAD Mutant Transgene Accelerates Amyloid Plaque Pathology in Tg2576 Transgenic Mice
Dineley et al (2002) J. Biol Chem. 277:22768-22780.
Fear Conditioningp
erc
en
t fr
ee
zin
g
Cued
pe
rce
nt
fre
ezi
ng
Context
2 Pairings
pe
rce
nt
fre
ezi
ng
Training
APP K670N, M671L n=9Double n=9
Wild Type n=9PS-1 M146L n=6
0
20
40
60
80
100
0 1 2 3 4 5 6 7
0
20
40
60
80
100
0 1 2 3 4 5 6
0
20
40
60
80
100
0 1 2 3 4 5
Dineley et al (2002) J. Biol Chem. 277:22768-22780.
Diagnosing AD
a: Neuritic Plaquesb: Diffuse Plaquesc: Neurofibrillary Tanglesd. Amyloid in blood vessel walls
Khachaturian and Radebaugh (1996). Boca Raton: CRC Press.
A
B
From Wang et al. (2000) The Journal of Biological Chemistry 275: 5626-5632.
The Cholinergic Hypothesis of AD
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