Why cancer survivors have a lower risk of Alzheimer disease

• Published in: Molecular genetics and metabolism Vol. 107; no. 3; pp. 630 - 631
• Main Author: Thinnes, Friedrich P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2012
• Subjects: ABC transporter; Alzheimer Disease - metabolism; Alzheimer Disease - prevention & control; Amyloid beta-Peptides - metabolism; Anion channels; ATP-Binding Cassette Transporters - metabolism; Biological Transport; Blood-Brain Barrier - metabolism; Cell Line; GxxxG; Humans; Multi drug resistance; Neoplasms - drug therapy; Neoplasms - metabolism; Neurons - metabolism; P-glycoprotein; Plasma lemma; Risk; Survivors; Voltage-Dependent Anion Channel 1 - metabolism; P-glycoprotein; Plasma lemma; Multi drug resistance; ABC transporter; Anion channels; GxxxG
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2012.06.016

Tying up two recent lines of experimental evidence may help explain this vital issue. On the one hand, data indicate that cancerous transformations of cells include changes in expression level and/or the functionality of multidrug resistance modulators which then disturb chemotherapy. On the other hand, studies have shown that some of the ABC transporters – at the blood–brain barrier – work as effective efflux pumps for amyloid Aβ peptides. Amyloid Aβ peptides, cut from the amyloid precursor protein of neurons can be assumed to induce brain wide neuronal apoptosis via opening plasma lemma-standing type-1 VDAC/porin channels as shown by in vitro experiments using established neuronal cell lines. However, extrusion of apoptosis inductive Aβ by increased ABC transporter activity at the blood–brain barrier from the brain of cancer survivors might abolish this effect. The hypothesis presented can be read as a clue on what in recent literature is referred to as the inverse association of cancer and Alzheimer disease.