Inflammation, antichymotrypsin, and lipid metabolism: autogenic etiology of alzheimer's disease

✍ Scribed by S. Janciauskiene; H.T. Wright

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 209 KB
• Volume: 20
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/(sici)1521-1878(199812)20:12<1039::aid-bies10>3.0.co;2-z

✦ Synopsis

Alzheimer's disease is a multifactor pathology, some of whose causes have been inferred from genetic studies, primarily of associated early-onset cases. Much evidence implicates the A␤ amyloid peptide as a neurotoxic agent, with chronic inflammation as an accompanying physiological contributor to the disease. The two central questions of how A␤ kills neurons and of the autogenic basis of disease remain unanswered. We hypothesize that specific interactions of A␤ with the inflammatory serpin, ␣ 1 -antichymotrypsin, abolish the serpin proteinase inhibitor activity and stimulate formation of the neurotoxic fibrillar form of A␤. Further, the fibrillar A␤ interacts with specific cell surface receptors, prompting its own biosynthesis and disrupting cellular cholesterol metabolism. These molecular and cellular interactions autogenically sustain the processes of A␤ formation, fibrillization, and receptor interaction, the last of which culminates in neuronal death through disruption of cholesterol metabolism. BioEssays 20:1039-1046.