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Alzheimer’s Disease. BRAIN, THE FINAL FRONTIER. Kiminobu Sugaya, Ph.D. Alzheimer’s Disease. NH 2. COOH. A . Plaques. Normal Secretory Pathway. Amyloid- b precursor protein. b -secretase. -secretase. g -secretase. -amyloid deposition. - PowerPoint PPT Presentation
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The Last FrontiersRobert Lyn Nelson
The Last FrontiersRobert Lyn Nelson
Alzheimer’s Alzheimer’s DiseaseDisease
BRAIN,THE FINAL FRONTIER
The Last FrontiersRobert Lyn Nelson
The Last FrontiersRobert Lyn Nelson
Kiminobu Sugaya, Ph.D.
Alzheimer’s Disease
Amyloid- precursor protein
NHNH22 COOHCOOHAA
-amyloid deposition-amyloid deposition
PlaquesPlaques
-secretase
Normal Normal Secretory Secretory PathwayPathway
-secretase-secretase
Mechanism of Neurodegeneration in Alzheimer’s Disease
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are needed to see this picture.
Glial Activation in Aging and Disease
Age
Glia
l Act
ivat
ion
(Inf
lam
mat
ion) Neuronal
Dysfunction or Neurodegeneration
ShiftShift
ShiftShift
APOPTOSISAPOPTOSIS
Cellular Fragmentation into Apoptotic Bodies
Phagocytosis and Degradation
DNA Fragmentation
Cromatin Condensation
Membrane Blebbing and Loss of Nuclear Envelope
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Aged Control
Fragmented DNA (Apoptosis) in the
hippocampusAlzheimer’s disease
Amyloid Plaque and Apoptosis
Plaque with many TUNEL positive cells
Plaque with many TUNEL positive cells
Plaque with a few TUNEL positive cellsPlaque with a few TUNEL positive cells
Plaque with no TUNEL positive
cells
Plaque with no TUNEL positive
cells
Neuro-fibrillary Tangles and Apoptosis
Astrocyte and Apoptosis
Apoptotic Cells
Astorocyte
GFAP mRNA GFAP mRNA Expression in the Expression in the
Aged Memory Aged Memory Impaired Model Rat Impaired Model Rat
14.6868.42122.16175.90229.64283.38337.13390.87444.61498.35552.09605.83659.57713.31767.05820.79874.54928.28982.021035.761089.501143.241196.981250.721304.461358.201411.941465.691519.431573.171626.911680.651734.39
Young
Aged unimpaired
Aged impaired
Ci/g tissue
memory score
Radi
o ac
tivi
ty in
the
sec
tion
(nC
i/g)
300
youngAged unimpaired Aged impaired
0
100
200
300
400
500
600
120 140 160 180 200 220 240 260 280
p=0.0001
Regression Analysis Regression Analysis of GFAP mRNA of GFAP mRNA
Expression in the Expression in the Hippocampus Hippocampus
against the Memory against the Memory ScoreScore
APP mRNA APP mRNA Expression in the Expression in the
Aged Memory Aged Memory Impaired Model Rat Impaired Model Rat
68.17176.38284.60392.81501.03609.24717.46825.67933.891042.101 150.311258.531366.741474.961583.171691.391799.601907.812016.032124.242232.462340.672448.892557.102665.322773.532881.742989.963098.173206.393314.603422.823531.03
Young
Aged unimpaired
Aged impaired
Ci/g tissue
1100
1200
1300
1400
1500
1600
1700
1800
1900
2000
120 140 160 180 200 220 240 260 280 300
memory score
Radi
o ac
tivi
ty in
the
sec
tion
(nC
i/g)
p = 0.0055
youngAged unimpaired Aged impaired
Regression Analysis Regression Analysis of APP mRNA of APP mRNA
Expression in the Expression in the Hippocampus Hippocampus
against the Memory against the Memory ScoreScore
Mn-SOD mRNA Mn-SOD mRNA Expression in the Expression in the
Aged Memory Aged Memory Impaired Model Rat Impaired Model Rat
Young
Aged unimpaired
Aged impaired
Ci/g tissue49.2852.1354.9757.8260.6663.5166.3669.2072.0574.8977.7480.5983.4386.2889.1291.9794.8297.66100.51103.35106.20109.04111.89114.74117.58120.43123.27126.12128.97131.81134.66137.50memory score
Radi
o ac
tivi
ty in
the
sec
tion
(nC
i/g)
90
110
130
150
170
190
210
120 140 160 180 200 220 240 260 280 300
p = 0.0190
youngAged unimpaired Aged impaired
Regression Analysis Regression Analysis of Mn-SOD mRNA of Mn-SOD mRNA Expression in the Expression in the
Hippocampus Hippocampus against the Memory against the Memory
ScoreScore
APP ISHH with GFAP Immunostaining in APP ISHH with GFAP Immunostaining in the Aged Memory Impaired Model Rats the Aged Memory Impaired Model Rats
matured
Aged Impaired Dentate GyrusHilus
Dentate Gyrus
Hilus
CA1
CA1
GFAP ISHH (astrocytes marker) with 4G8 (A) Immuno-histochemistry in PS1-APP
TM
APP ISHH with GFAP Immuno-APP ISHH with GFAP Immuno-histochemistry (astrocytes marker) in PS1-histochemistry (astrocytes marker) in PS1-APP TMAPP TM
APP ISHH with 4G8 (A) Immuno-histochemistry in PS1-APP TM
