The Trigger for Alzheimer’s

By understanding the role of AChE-peptide, Neuro-Bio can explain, for the first time, where and why neurodegeneration is initiated by highlighting action of AChE-peptide as a characteristic, selective feature of the vulnerable “hub” cells. Neuro-Bio can also show how calcium entry, triggered by AChE-peptide, leads to an intracellular cascade promoting production of beta-amyloid and tau. Once this cascade is underway both beta-amyloid and AChE-peptide act as toxic molecules at adjacent but distinct sites at the alpha-7 receptor perpetuating further cell death by triggering production of more AChE, in turn leading to more beta-amyloid, and vice versa. This promotes more target receptors and a feed-forward cycle of still more calcium influx as well as accumulation of beta-amyloid and tau.

The vulnerable cells forming the ‘hub’ originate from a distinct part of the early embryo brain; the basal plate whereas other brain cells derive from the alar plate. Unlike all other brain cells the ‘hub’ cells retain sensitivity to developmental chemicals usually only released, and beneficial, in the developing brain (see Figure below). When compared to developing foetal/neonatal brain cells, mature, adult brain cells respond differently to the same developmental chemicals, which if released inappropriately in maturity as a result of brain damage in the different, mature brain landscape, are toxic causing cell death instead of assisting in brain cell development (see Figure below). This brain cell damage causes additional release of the now toxic chemical in the mature brain and the relentless cycle of neurodegeneration (see Figure below).

Figure that illustrates the cascade of actions that begin the cycle of cell death in the ‘hub’ neurons and subsequently further brain cell death along with the production of beta-amyloid and tau. This scheme also accounts for the selective cell death that occurs in Alzheimer’s Disease. The neonatal young brain is characterised by the ability to be shaped by various growth factors. However, once mature, most of the standard brain cells lose their sensitivity to these chemicals. If they are damaged, as in a stroke, some die whilst other compensate, leading to partial or complete recovery of function.

At first this pernicious cycle continues without detectable symptoms but eventually cell loss in the ‘hub’ neurons becomes extensive and their normal target areas in the cortex begin to show effects of depravation of normal active input (trans-synaptic degeneration). Cognitive impairments will be manifest and more widespread physical damage finally becomes apparent as neurons die (see Figure below).

Using the knowledge Neuro-Bio has gained in its’ research it has discovered the single, key, mechanism underlying the initial response of the characteristic neurodegeneration to such triggers as a blow to the head / ischaemia / rise in free radicals as can occur in ageing.