char = B;code = 66
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = a;code = 97
char = m;code = 109
char = y;code = 121
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = :;code = 58
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = A;code = 65
char = P;code = 80
char = P;code = 80
char = N;code = 78
char = L;code = 76
char = H;code = 72
char = /;code = 47
char = N;code = 78
char = L;code = 76
char = H;code = 72
char = ;code = 32
char = X;code = 88
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = -;code = 45
char = 1;code = 49
char = P;code = 80
char = 2;code = 50
char = 6;code = 54
char = 4;code = 52
char = L;code = 76
char = /;code = 47
char = P;code = 80
char = 2;code = 50
char = 6;code = 54
char = 4;code = 52
char = L;code = 76
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = z;code = 122
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ';code = 39
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
result sql = Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease.
Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease.
char = A;code = 65
char = l;code = 108
char = z;code = 122
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ';code = 39
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = z;code = 122
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ';code = 39
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = A;code = 65
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = y;code = 121
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = z;code = 122
char = y;code = 121
char = g;code = 103
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = z;code = 122
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ';code = 39
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = y;code = 121
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = 2;code = 50
char = 6;code = 54
char = 4;code = 52
char = L;code = 76
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = A;code = 65
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char = z;code = 122
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ';code = 39
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char = d;code = 100
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
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char = i;code = 105
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char = p;code = 112
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char = s;code = 115
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = W;code = 87
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char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = A;code = 65
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
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char = o;code = 111
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char = i;code = 105
char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = d;code = 100
char = o;code = 111
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char = b;code = 98
char = l;code = 108
char = e;code = 101
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char = k;code = 107
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char = o;code = 111
char = c;code = 99
char = k;code = 107
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = b;code = 98
char = e;code = 101
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char = i;code = 105
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char = n;code = 110
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char = a;code = 97
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char = ;code = 32
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char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = l;code = 108
char = l;code = 108
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char = l;code = 108
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char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
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char = A;code = 65
char = b;code = 98
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char = a;code = 97
char = 1;code = 49
char = -;code = 45
char = 4;code = 52
char = 0;code = 48
char = /;code = 47
char = 1;code = 49
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char = 4;code = 52
char = 2;code = 50
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = r;code = 114
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char = i;code = 105
char = n;code = 110
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char = h;code = 104
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char = o;code = 111
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char = f;code = 102
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char = o;code = 111
char = m;code = 109
char = ;code = 32
char = 3;code = 51
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char = ,;code = 44
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char = -;code = 45
char = ,;code = 44
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char = 9;code = 57
char = -;code = 45
char = ,;code = 44
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char = 1;code = 49
char = 2;code = 50
char = -;code = 45
char = ,;code = 44
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char = a;code = 97
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result sql = Alzheimer's disease is a multifactorial, progressive, age-related neurodegenerative disease. In familial Alzheimer's disease, Abeta is excessively produced and deposited because of mutations in the amyloid precursor protein, presenilin-1, and presenilin-2 genes. Here, we generated a double homozygous knock-in mouse model that incorporates the Swedish familial Alzheimer's disease mutations and converts mouse Abeta to the human sequence in amyloid precursor protein and had the P264L familial Alzheimer's disease mutation in presenilin-1. We observed Abeta deposition in double knock-in mice beginning at 6 months as well as an increase in the levels of insoluble Abeta1-40/1-42. Brain homogenates from 3-, 6-, 9-, 12-, and 14-month-old mice showed that protein levels of manganese superoxide dismutase (MnSOD) were unchanged in the double knock-in mice compared to controls. Genotype-associated increases in nitrotyrosine levels were observed. Protein immunoprecipitation revealed MnSOD as a target of this nitration. Although the levels of MnSOD protein did not change, MnSOD activity and mitochondrial respiration decreased in knock-in mice, suggesting compromised mitochondrial function. The compromised activity of MnSOD, a primary antioxidant enzyme protecting mitochondria, may explain mitochondrial dysfunction and provide the missing link between Abeta-induced oxidative stress and Alzheimer's disease.

Publication: Am. J. Pathol. 2006 May ;168(5)::1608-18.
Publication Date: 2006 May
Study Author(s): Anantharaman, Muthuswamy;Tangpong, Jitbanjong;Keller, Jeffery N;Murphy, Michael P;Markesbery, William R;Kiningham, Kelley K;St Clair, Daret K;
Institution: Graduate Center for Toxicology, University of Kentucky, Lexington 40536-0305, USA.
Shortcut link to this study:
Alzheimer's disease is a multifactorial, progressive, age-related neurodegenerative disease. In familial Alzheimer's disease, Abeta is excessively produced and deposited because of mutations in the amyloid precursor protein, presenilin-1, and presenilin-2 genes. Here, we generated a double homozygous knock-in mouse model that incorporates the Swedish familial Alzheimer's disease mutations and converts mouse Abeta to the human sequence in amyloid precursor protein and had the P264L familial Alzheimer's disease mutation in presenilin-1. We observed Abeta deposition in double knock-in mice beginning at 6 months as well as an increase in the levels of insoluble Abeta1-40/1-42. Brain homogenates from 3-, 6-, 9-, 12-, and 14-month-old mice showed that protein levels of manganese superoxide dismutase (MnSOD) were unchanged in the double knock-in mice compared to controls. Genotype-associated increases in nitrotyrosine levels were observed. Protein immunoprecipitation revealed MnSOD as a target of this nitration. Although the levels of MnSOD protein did not change, MnSOD activity and mitochondrial respiration decreased in knock-in mice, suggesting compromised mitochondrial function. The compromised activity of MnSOD, a primary antioxidant enzyme protecting mitochondria, may explain mitochondrial dysfunction and provide the missing link between Abeta-induced oxidative stress and Alzheimer's disease.
PMID: 16651627

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