Hardy J, Allsop.
Amyloid deposition as the central event in the aetiology of Alzheimer's disease.
Trends Pharmacol Sci. 1991 Oct;12(10):383-8.
While there may be many causes of Alzheimer's disease (AD), the same pathological sequence of events, described here by John Hardy and David Allsop, is likely to occur in all cases. The recent discovery of a pathogenic mutation in the b-amyloid precursor protein (APP) gene on chromosome 21 suggests that APP mismetabolism and b-amyloid deposition are the primary events in the disease process. The occurrence of AD in Down's syndrome is consistent with this hypothesis. The pathological cascade for the disease process is most likely to be: b-amyloid deposition—tau phosphorylation and tangle formation—neuronal death. The development of a biochemical understanding of this pathological cascade will facilitate rational design of drugs to intervene in this process.