Since the Wischik team first discovered nearly 20 years ago that neurofibrillary tangles are made up of Tau protein, it has been a leading proponent of the Tau aggregation hypothesis and maintains the position that Tau aggregation makes a direct contribution to dementia, irrespective of Amyloid ß-load in the brain.

The Wischik team discovered how the aggregation of Tau is directly linked both to clinical dementia and cell death. It found that Tau aggregation is driven by an autocatalytic process described by the Tau aggregation cascade which results in the neurofibrillary tangles discovered by Dr. Alois Alzheimer.

Neurofibrillary tangles are intraneuronal clusters of aberrant Tau protein polymers that consist of paired helical filaments (PHFs), thus termed from their characteristic double-twisted ribbon shape.

The polymerization of Tau protein in the aggregation cascade diverts Tau proteins from their normal function and forces the cell to utilize significant resources both to compensate for Tau loss and to deal with the intrinsic toxicity of the Tau polymers that build up within the neuron.

The load of Tau aggregates in the brain is highly correlated with clinical dementia, as they obstruct the cell’s energy-producing apparatus (mitochondria), its protein synthesis apparatus (the endoplasmic reticulum), and its transport apparatus .

The Wischik team found that at a more advanced stage, Tau aggregation leads to the formation of Neurofibrillary Tangles, Tau and Amyloid ß plaques and eventual cell death.

To confirm the validity of the Tau aggregation hypothesis, the Wischik team developed proprietary Tau-transgenic animal models and proved that Tau aggregation alone is sufficient to produce a cognitive defect, and that blocking the Tau aggregation reverses this defect.

The role of Tau aggregation in Alzheimer’s disease has now been decisively validated further by the Company’s Phase 2 trial results, showing that rember™, the first TAI (Tau aggregation inhibitor) ever tested clinically, stabilises the progression of Alzheimer’s disease.