Scientific Basis for Tau Aggregation Inhibition
In 1991, Professor Heiko Braak of Germany and his wife reported a tool that directly measured the development of Alzheimer’s related pathology in patients. Braak graded the presence, distribution and density of tau tangles in the brain and defined six distinct stages of Alzheimer’s progression (Braak stages).
The TauRx research team built on the findings of the Braaks and demonstrated, in a clinical setting, a strong correlation between the degree of tau protein neurofibrillary pathology in the brain as measured using Braak staging, the amount of aggregated tau in pre-tangle brain regions and the degree of cognitive incapacitation as measured by scores on the mini mental state exam (MMSE). The Braak neuropathological staging system for Alzheimer’s disease provides a way to directly measure the relationship between tau aggregate formation and cognitive decline [loss of memory].
Clinical Progression Correlates to Braak Stage
- The spread of tau protein aggregates in the brain correlates with clinically observed cognitive deficit and progression of functional brain scan deficit.
- The pattern of distribution and the density of tau protein aggregates throughout the brains of Alzheimer’s patients are very similar.
- Neurofibrillary tangles first form in the medial temporal lobe regions of the brain, then spread into the limbic and neocortical regions.
- The basis for this neuroanatomical spread has been established recently in mouse models where abnormal tau can be exchanged between neurons. In effect, the early stage aggregates of tau (oligomers) act as infectious particles, spreading the pathology from one brain region to the next.
- The tau aggregation cascade, once initiated inside a neuron, is self-replicating, consuming the normal tau pool in the cell, and converting it to toxic aggregates which continue to accumulate to the point of destruction of the neuron. By end-stage, there is almost complete conversion of normal tau protein into the aggregated form.
Braak and Braak. (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239-259.