Retrospectacle: A Neuroscience Blog

Before I became interested in hearing research, I thought I was going to spend my career studying Alzheimer’s disease (AD), and worked at the Roskamp Institute for Neurodegenerative Disorders at USF. AD is a major enigma in medicine due to the many contributing factors: genetic, lifestyle, and environmental; as well as differing times of onset (early and late) and varying symptoms among affected individuals. The end result is clear though: AD is fatal and affects the brain in drastic ways. AD is characterized by a few pathological hallmarks at the neural level. One is the presence of amyloid-beta plaques which are an abnormally-processed form of a normal precursor protein. These plaques are sticky and are thought to be neurotoxic. The other hallmark is neurofibrillary tangles made up of a protein called tau, found inside the affected neurons. These tangles aggregate into an insoluble mass, however it is still unknown whether tau tangles contribute to the pathology of AD or are a downstream product of it.

Over the past 10 years, quite a few research groups have focused on vaccines aimed at preventing either the improper formation of amyloid-beta plaques or of tau tangles. Recently, a vaccine has proven successful in preventing tau tangles in mice who were genetically engineered to produce high levels of tau. The study describing the vaccine was published in the August 22nd Journal of Neuroscience.

The vaccine prompted the immune system to produce antibodies that could enter the brain and bind to abnormal tau, the researchers said. This prevented tau from forming harmful tangles and causing motor coordination problems in the mice.

The resulting loss of motor coordination was significantly reduced in those immunized with a specific piece of the detrimental tau protein. By producing antibodies that could enter the brain and bind to irregular tau, the immune system prevented their harmful aggregation and associated behavioral impairments. These artificial tau fragments are studded with phosphate groups which are present in the harmful version of tau and promote aggregation. The antibodies generated by the vaccine will bind only to the abnormal type of tau, leaving the normal version, which has important biologic functions.