Vol.64

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.63

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.62

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.61

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.60

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.59

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.58

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.57

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.56

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.55

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.54

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12
• Supplement

Vol.53

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

Vol.52

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

Vol.51

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

Vol.50

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

Vol.49

• No.1
• No.2/3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

Vol.48

• No.1
• No.2
• No.3
• No.4
• No.5
• No.6
• No.7
• No.8
• No.9
• No.10
• No.11
• No.12

• Vol.47 to 1
  (Members Only)

• HOME
• Vol.44 No.11
• CLINICA NEUROL, 44: 768−770, 2004
• Vol.44 No.11 contents

The 45th Annual Meeting of the Japanese Society of Neurology

Pathogenesis of Alzheimer's disease: implications from amyloid research front

Takeshi Iwatsubo, M.D.

Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo

Deposition of amyloid β peptides as senile plaques is a hallmark lesion of Alzheimer's disease that is implicated in its pathogenesis. Aβ is produced from amyloid precursor protein by sequential cleavages by β- and γ-secretases. γ-Secretase is a membrane protease complex harboring presenilin as a catalytic subunit. Recent studies revealed how presenilin is assembled with its cofactor proteins and acquires the γ-secretase activity: Aph-1 and nicastrin initially form a subcomplex to bind and stabilize presenilin, and then Pen-2 confers the γ-secretase activity and facilitates endoproteolysis of presenilin. Understanding the mechanism of γ-secretase cleavage will help to clarify how intercellular cell signaling through transmembrane proteins are regulated by intramembrane proteolysis, and eventually to cure Alzheimer's disease by inhibiting secretases.

(CLINICA NEUROL, 44: 768−770, 2004)
key words: Alzheimer's disease, β-amyloid, Aβ, presenilin, γ-secretase

(Received: 12-May-04)