Protein Mutations Associated with Alzheimer’s Linked to Cancer Risk
Along with its well-recognized part in neurodegeneration, tau engages in maintenance of genome stability and chromosome integrity.
Specifically, peripheral cells in patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (hereditary tauopathies), in addition to cells in animal models, reveal chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward strange recombination.
Now, a team from IRCCS Foundation Carlo Besta Neurological Institute in Milan has uncovered a new role for mutated tau protein as a potential risk factor in the development of cancer.
“Our study revealed that the presence of tau mutations raises the risk of developing cancer,” said Fabrizio Tagliavini, MD, scientific director, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.
“Furthermore, our bioinformatic analysis highlighted a broader functional environment for the tau protein, which had been previously associated mainly with disease development in the context of neurodegeneration.”
“A mutated tau has a reduced ability to bind to microtubules; this leads to microtubule destabilization and cytoskeleton disruption, which is detrimental to cellular survival,” explained Tagliavini. “Additionally, free tau protein can form toxic aggregates within nerve cells, impairing neuronal function.”
Previous work in the Tagliavini lab demonstrated
how mutations in these proteins led to chromatin defects and chromosome abnormalities. “It is well-known that chromosome aberrations are often linked to cancer,” said Tagliavini. “Therefore, we decided to determine if there was a possible association between tau mutations and cancer.”The team examined cancer incidence at 15 households bearing seven distinct tau mutations and influenced by FTLD. To compute cancer risk, each tau-mutated family was paired with three benchmark households using superimposable pedigrees (control subject’s age, sex, and native place fitting the individual changed with FTLD).
Fifteen percent of subjects of the study in tau-mutated families developed cancer, while 9 percent from reference households had cancer. Cancer forms in both cohorts were changeable; tau mutations weren’t associated with particular cancers.
After multivariate analysis, the investigators determined that people from tau-mutated households were 3.72 times more likely to develop cancer when compared with the reference households. The researchers used a bioinformatics study to comprehend the connections of tau protein with other proteins.
“Patients carrying tau mutations are usually attended for neurodegeneration,” said Tagliavini. “However, with further confirmation of our results, these patients could also be monitored for their risk of developing cancer. Clinicians should take into account both of these aspects of tau pathology.”
