Low levels of a specific protein may cause Alzheimer's

Low levels of a specific protein may cause Alzheimer's

The researchers have determined that the protein SIRT6 is almost completely absent in Alzheimer's disease patients and likely contributes to its onset.

The common consensus is that aging is the result of DNA damage accumulation -- essentially the body's failure to implement processes to completely repair its DNA.

According to the study, published in Cell Reports, one of the key components in this DNA repair process is the protein SIRT6. The researchers have determined in mouse models that high levels of SIRT6 facilitate DNA repair while low levels enable DNA damage accumulation.

Researchers show that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death, and hyperphosphorylated Tau—a critical mark in several neurodegenerative diseases.

Mechanistically, SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3α/β. Finally, SIRT6 mRNA and protein levels are reduced in patients with Alzheimer’s disease. 

The researchers also tested their hypothesis on neurodegenerative diseases besides Alzheimer's, and found that a deficiency of the SIRT6 protein was also present in patients.

According to lead author, "If a decrease in SIRT6 and lack of DNA repair is the beginning of the chain that ends in neurodegenerative diseases in seniors, then we should be focusing our research on how to maintain production of SIRT6 and avoid the DNA damage that leads to these diseases."