Amyloid Cascade Hypothesis - Institute of Psychiatry Wiki …

Figure 4:This figure shows a simplification of the cascade of events that occur in Alzheimer's disease as predicted by the Amyloid Hypothesis. (Karran, 2011).

The Amyloid Cascade Hypothesis of Alzheimer's Disease?

The hypothesis that Alzheimer’s is caused by plaques and tangles in the brain is not accepted by all scientists. In a 2009 article in the Journal of Alzheimer’s Disease, a group of researchers stated that the popular hypothesis that beta amyloid causes dementia is mistaken and because this flawed hypothesis Alzheimer’s drugs continue to fail in clinical trials.

The amyloid cascade hypothesis for Alzheimer's …

It is clear from above that many cell processes are disrupted in AD and they are initiated by different events. Consequently, any hypothesis that explains AD has to incorporate the idea of multiple primary lesions to a possible single mode of pathogenesis. The Amyloid Cascade Hypothesis was proposed in 1991 by John Hardy and David Allsop (reviewed by ). This hypothesis suggested that the mismetabolism of APP was the initiating event in AD pathogenesis, subsequently leading to the aggregation of Aβ, specifically Aβ42. Formation of neuritic plaques would instigate further pathological events, including the formation of NFTs, NTs and disruption of synaptic connections, which would lead to a reduction in neurotransmitters, death of tangle-bearing neurons and dementia ( ).

The biochemistry of Alzheimer's disease ..

A 2004 study found that deposition of amyloid plaques does not correlate well with neuron loss. This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies. When this occurs, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells. Herpes simplex virus type 1 has also been proposed to play a causative role in people carrying the susceptible versions of the apoE gene.

The amyloid hypothesis of Alzheimer's disease: …

To summarize, Alzheimer's Disease is a very common case of dementia that has significant implications the future health and well being of elderly patients. Currently, the most accepted hypothesis by scientists is the Beta-amyloid hypothesis which describes possible processing faults involved with the Amyloid Precursor Protein (APP) causing degradation of brain tissue. In most cases, epidemiology shows that age is a main factor for Alzheimer's disease to appear. Characterized by a loss of cognitive function, this debilitating disease unfortunately has no forms of prevention other than eating foods that boost cognitive functions and brain activity. In terms of future research, a novel treatment that has recently been discovered is the use of immunization to stop the development of the disease. Through techniques of active or passive immunization, the administration of antibodies causes alterations and improvement in the beta-amyloid plaques. With such a high onset rate at relatively high ages, future scientific research will be essential to continue to find new preventative measures and more effective treatments.

KIN450-Neurophysiology - Alzheimer’s

Karran, E., Mercken, M., & Strooper, B. D. (2011). The amyloid cascade hypothesis for Alzheimer's disease: An appraisal for the development of therapeutics. Nature Reviews Drug Discovery Nat Rev Drug Discov,10(9), 698-712.