Paradigm shift redefining molecular, metabolic and structural events in Alzheimer’s disease involves a proposed contribution by transition metals. Defined lengthy preclinical stage provides new hope to circumvent advancement of disease-and age-related neurodegeneration.

Author: Cavaleri F.

Source: Medical Hypotheses.

Year: 2015

Comment:

Abstract / Excerpt:

It is estimated that 5.5 Million North Americans suffer from varying degrees of Alzheimer’s disease (AD) and by the year 2050 it may be one in 85 people globally (100 Million). It will be shown that heavy metal toxicity plays a significant role in sporadic AD. Although current literature speaks to involvement of metal ions (via Fenton reaction), studies and reviewers have yet to link cellular events including known structural changes such as amyloid plaque development to this metal toxicity the way it is proposed here. Contrary to the current AD model which positions BACE1 (β-secretase) as an aberrant or AD-advancing enzyme, it is proposed herein that the neuron’s protective counteraction to this metal toxicity is, in fact, a justified increase in BACE1 activity and amyloid precursor protein (APP) processing to yield more secreted APP (sAPP) and β-amyloid peptide in response to metal toxicity. This new perspective which justifies a functional role for APP, BACE1 enzyme activity and the peptide products from this activity may at first appear to be counterintuitive. Compelling evidence, however, is presented and a mechanism is shown herein that validate BACE1 recruitment and the resulting β-amyloid protein as strategic countermeasures serving the cell effectively against neuro-impeding disease.

Citation: Cavaleri F. Paradigm shift redefining molecular, metabolic and structural events in Alzheimer’s disease involves a proposed contribution by transition metals. Defined lengthy preclinical stage provides new hope to circumvent advancement of disease-and age-related neurodegeneration. Medical Hypotheses. 2015; 84(5):460-9.