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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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Presentation on theme: "Aging-Related Memory Disorders Alzheimer’s Disease From Mechanisms of Memory by J. David Sweatt, Ph.D."— Presentation transcript:

1 Aging-Related Memory Disorders Alzheimer’s Disease From Mechanisms of Memory by J. David Sweatt, Ph.D.

2 Amyloid Plaques and Neurofibrillary Tangles Image by Poul Jorgensen, Claus Bus, Niels Pallisgaard, Marianne Bryder, and Arne Lund Jorgensen

3 A B C Terminus N Terminus Crystal Structure of Amyloid Beta Peptide Watson et al (1998) Biochemistry 37:12700- 12706.

4  Amyloid Precursor Protein (APP) Price, Sisodia and Borchelt (1998) Science 282:1079-1083.

5 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.

6 Fear Conditioning percent freezing Cued percent freezing Context 2 Pairings percent freezing Training APP K670N, M671L n=9 Double n=9 Wild Type n=9 PS-1 M146L n=6 0 20 40 60 80 100 01234567 0 20 40 60 80 100 0123456 0 20 40 60 80 100 012345 Dineley et al (2002) J. Biol Chem. 277:22768-22780.

7 Diagnosing AD a: Neuritic Plaques b: Diffuse Plaques c: Neurofibrillary Tangles d. Amyloid in blood vessel walls Khachaturian and Radebaugh (1996). Boca Raton: CRC Press.

8 A B From Wang et al. (2000) The Journal of Biological Chemistry 275: 5626-5632. The Cholinergic Hypothesis of AD


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