Amyloid beta and Tau—two proteins – are central to the pathology of Alzheimer’s disease. Now, a recent study published in Science has come out with findings about these two proteins that are very important not only from the treatment perspective, but also for our understanding so far. The Science study says that both Amyloid beta and Tau proteins can act like prions—misfolded proteins that are lethal and can spread through tissues like any other infection in the body – in Alzheimer’s disease. The study has a striking conclusion that the prion conformers of these proteins are strongly associated with the age of the patients—its levels are higher in patients that died at younger age than those who died in older age.
The researchers conducted post mortem on brain tissues from 75 Alzheimer’s patients. They combined two recently developed laboratory tests to measure the prions in human tissues rapidly—a new amyloid beta detection system developed in the Prusiner lab and a Tau protein assay developed by Marc Diamond. The earlier methods to measure prion levels would take months to reveal the levels of prions, but the new methods could measure the infectious prions in just three days. The brain tissues were collected from over 100 patients that died of Alzheimer’s disease and other neurodegenerative diseases from United States, Europe and Australia.
Out of the brain samples that were subjected to post mortem, 75 Alzheimer’s disease brains showed elevated levels of both Amyloid beta and Tau proteins; 11 samples from patients with cerebral amyloid angiopathy (CAA), only amyloid beta prions could be observed; and in 10 samples from patients with fromtotemporal lobar degeneration (FTLD) only Tau prions were detected. The CAA and the FTLD are both neuro-degenerative conditions and cause dementia like symptoms.
The most remarkable finding of the study is that the prion forms of both Amyloid Beta and Tau proteins are present in formidably higher levels among the patients who died in early ages. Particularly, when they compared the overall Tau build up, the researchers found that the relative abundance of prion Tau in aged Alzheimer’s brains decrease exponentially. Relative to the overall Tau levels, the Tau prion levels in a patient that died at the age of 40 were averagely 32 times higher than a patient who died at 90.
What Are Prions?
Prions are the proteins which have aberrations in shape in comparison to the normal 3D structure of the protein. First discovered in the Mad Cow disease, such misshapen proteins can act like other infectious agents like that of virus and bacteria, i.e. it could spread in the body. Prions do this by affecting the normal proteins of same kind to have the misfolded shape. They still remain something of an enigma to the scientific world. Especially, what exactly causes a protein to take up the aberrant structure that makes it a prion is still elusive for the researchers.
Prions are primarily involved in neurodegeneration in humans and other animals. The Creutzfeldt Jakob disease (CJB) in humans and Bovine Spongiform Encephalopathy (BSE)—commonly known as mad cow disease in cattle are related to prions.
What makes the prions dangerous is their ability to get transferred from individual to individual or from species to species. The CJB in humans was mainly due to consumption of beef having the mad cow disease. Moreover, prions are also extremely enduring; even heating them at very elevated temperatures could only only lead to their death after much difficulty.
Now, the knowledge of their involvement in Alzheimer’s disease can open up new avenues in understanding the progression and treatment of the disease.