Amyloid cascade hypothesis

Figure 1 Amyloid cascade hypothesis and intervention points.

Hardy, J.A. and Higgins, G.A., Alzheimer s disease the amyloid cascade hypothesis, Science, 256,184,1992. 

Amodiaquine, metabolism of, 570, 571 Amyloid cascade hypothesis, 68 Amyloid deposits, 77-78 Aneurysm rupture, 380 Angiogenesis, 220... 

Figure 12 Amyloid cascade hypothesis (modified after Hardy and Selkoe, 2002. Reprinted with permission. American Association for the Advancement of Science) Cholesterol is thouc it to be involved in the formation of f-amyloid (AP) in the brain. Inhibitors of cholesterol formation could then prevent the formation of (neurotoxic) amyloid.

Amyloid cascade hypothesis of Alzheimer s disease. A leading contemporary theory for the biological basis of Alzheimer s disease centers around the formation of beta amyloid. Certainly much of this amyloid destroys cholinergic neurons in the nucleus basalis of Meynert (Fig. 12—11), although the damage becomes more widespread as the disease progresses (Fig. 12-13). Hypothetically, Alzheimer s disease is a disorder in which beta amyloid deposition destroys neurons, in a manner somewhat analogous to that in which the abnormal deposition of cholesterol causes atherosclerosis. Thus,... 

Another version of the amyloid cascade hypothesis is the possibility that something is wrong with a protein that binds to amyloid and removes it (Figs. 12—21... 

FIGURE 12—17. The amyloid cascade hypothesis of Alzheimer s disease (part 2). Once altered amyloid precursor protein (APP) is formed (Fig. 12-16), it leads to the formation of beta amyloid deposits. 

FIGURE 12—21. Another version of the amyloid cascade hypothesis is the possibility that something is wrong with a protein that binds to amyloid and removes it. This protein is called APO-E. In the case of "good" APO-E, it binds to beta amyloid and removes it, preventing the development of Alzheimer s disease and dementia. 

To review the neuropathology of Alzheimer s disease, and its relationship to the amyloid cascade hypothesis and the glutamate excitotoxic hypothesis of Alzheimer s disease. 

The amyloid cascade hypothesis of Alzheimer s disease states that ... 

Lee H. G., Casadesus G., Zhu X. W., Takeda A., Perry G., and Smith M. A. (2004). Challenging the amyloid cascade hypothesis - Senile plaques and amyloid-beta as protective adaptations to Alzheimer disease. In DeGrey A. D. N. (ed.), Strategies for Engineered Negligible Senescence Why Genuine Control of Aging May Be Foreseeable. Annals of the New York Academy of Sciences New York Acad Sciences, pp. 1-4. 

Sommer B. Alzheimer s disease and the amyloid cascade hypothesis Ten years on. Curr Opin Pharmacol 2002 2(l) 87-92. 

Epidemiological studies have shown that mutations in APP and presenilin genes are linked to rare familial and early-onset forms of AD (2). This observation led to the amyloid cascade hypothesis suggesting that excessive AB production is the primary cause of the disease. 

Extracellular accumulation of Af) represents the foundation of the amyloid cascade hypothesis. The importance of intracellular A accumulation in the pathogenesis of AD has emerged as a possibility in recent studies (LaFerla et al., 2007). These studies, implemented in human and mouse brains were made possible by the development of antibodies that could differentiate A O and Af)42 from the transmembrane amyloid precursor protein from which they derived (Gouras et al.,... 

Lee HG, Casadesus G, Zhu X, Takeda A, Perry G, Smith MA (2004) Challenging the amyloid cascade hypothesis senile plaques and amyloid-beta as protective adaptations to Alzheimer disease. Ann N Y Acad Sci 1019 1-4... 

Snowdon DA, Kemper SJ, Mortimer JA, Greiner LH, Wekstein DR, Markesbery WR (1996) linguistic ability in early life and cognitive function and Alzheimer s disease in late Rfe. Findings from the Nun Study. J Am Med Assoc 275 528-532 Sommer B (2(X)2) Alzheimer s disease and the amyloid cascade hypothesis ten years on. Curr Opin Pharmacol 2 87-92... 

Hardy JA, Higgins GA (1992) Alzheimer s disease The amyloid cascade hypothesis. Science 256 184—185. 

The biological activity, if any, of sAPPjS is so far unknovm. The role or contribution of N-truncated Aj3 (p3, for example) to AD is the subject of a hotly contested debate, entitled the shorter amyloid cascade hypothesis (87,105). 

Korczyn AD (2008) The amyloid cascade hypothesis. Alzheimers Dement 4 176-178... 

Hardy J (2006) Has the amyloid cascade hypothesis for Alzheimer s been proved Curr Alzheimer Res 3 71-73... 

It has been known for several years that APP may play an important role in patients with AD. Some think that plaque formation triggers the disease and that tangles are a secondary effect. This is known as the amyloid-cascade hypothesis. 

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