aging-related memory disorders alzheimer’s disease from mechanisms of memory by j. david sweatt,...
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Aging-Related Memory Disorders
Alzheimer’s Disease
From Mechanisms of Memory by J. David Sweatt, Ph.D.
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Amyloid Plaques and Neurofibrillary Tangles
Image by Poul Jorgensen, Claus Bus, Niels Pallisgaard, Marianne Bryder, and Arne Lund Jorgensen
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A
B
C Terminus
N Terminus
Crystal Structure of Amyloid Beta Peptide
Watson et al (1998) Biochemistry 37:12700-12706.
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Amyloid Precursor Protein (APP)
Price, Sisodia and Borchelt (1998) Science 282:1079-1083.
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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.
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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
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0 1 2 3 4 5 6 7
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0 1 2 3 4 5 6
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0 1 2 3 4 5
Dineley et al (2002) J. Biol Chem. 277:22768-22780.
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Diagnosing AD
a: Neuritic Plaquesb: Diffuse Plaquesc: Neurofibrillary Tanglesd. Amyloid in blood vessel walls
Khachaturian and Radebaugh (1996). Boca Raton: CRC Press.
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A
B
From Wang et al. (2000) The Journal of Biological Chemistry 275: 5626-5632.
The Cholinergic Hypothesis of AD