The new study shows for the first time that the immune system can combat the pathological form of tau protein.
The study used mice that were genetically engineered to produce abnormal tau proteins early in life. These became entangled in several regions of the central nervous system. 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 behavioural impairments.
Alzheimer’s disease is associated with neurons in the memory centre of the brain becoming choked by the buildup of two types of proteins: tau, which turns destructive when it is prone to forming fibrous tangles, and amyloid beta. “It’s likely that there’s a synergism in the pathology,” said Einar Sigurdsson Ph.D., Assistant Professor of Psychiatry and Pathology at New York University School of Medicine. “Amyloid pathology may cause tau pathology and tau pathology might cause more amyloid pathology.”
The therapeutic approach is based on using fragments of abnormal tau protein as a vaccine. These fragments are studded with phosphate groups, which are thought to promote the aggregation of tau. The antibodies generated by the vaccine are therefore likely to bind to abnormal tau and promote its breakdown. Normal tau, which would be far less affected, has such important biological functions as facilitating transport of chemicals within neurons and maintaining their structure.
The transgenic mice in the new study were predisposed to forming tau tangles early in life. Although a decline in motor abilities had progressed by eight months, the mice still remained healthy enough to walk, feed and attempt simple behavioural tasks. But the mice did not undergo thorough cognitive testing.
The battery of behavioural tests at five and eight months of age showed that immunized mice performed better — they travelled faster during exploratory activity, exhibited better balance on a rotating rod and committed less foot-slips while traversing a narrow wooden beam. These mice were also found to have less tau protein tangles in the brain.
MEDICA.de; Source: New York University Medical Center