Editors' Note: Friedrich Thinnes proposes an interesting hypothesis for the association between skin cancer and reduced Alzheimer disease risk. Willey critiques the statistical methods in the study by Martínez-Sánchez et al. on statins and stroke severity. However, both parties agree that no definite conclusion can be made before a clinical trial on acute treatment of stroke patients with statins is completed. Martin discusses his experience with trigger factors in migraine and points out to Hougaard et al. that triggers have been studied in the past, contrary to the authors' claim. —Chafic Karam, MD, and Robert C. Griggs, MD
I propose a biologically based hypothesis for the association between skin cancer and reduced Alzheimer disease (AD) risk.1 Amyloid Aβ peptides, cut from the amyloid precursor protein of neurons, are assumed to induce brain-wide neuronal apoptosis via opening plasma lemma-standing type 1 voltage-dependent anion channels (VDAC). This process results in AD whenever critical brain regions are affected.2,–,4 Either reaction partner carries one or several GxxxG motifs. Furthermore, data indicate that amyloid Aβ peptides can be extruded from the brain by ABC transporters at the blood–brain barrier and cancerous transformations accompany changes in the expression level or the functionality of multidrug resistance modulators that then disturb chemotherapy.5 However, enhanced extrusion of apoptogenic amyloid A by raised ABC transporter activities of cancer survivors might diminish or even abolish intrabrain apoptotic effect. These findings, along with other data,5 may explain why cancer survivors have a lower risk of AD. Finally, the VDAC/amyloid interaction model of AD pathogenesis could explain the reverse relationship of AD and cancer.5
- © 2013 American Academy of Neurology
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