Studies have shown that amyloid beta accumulation in the brain does not correlate with the level of dementia. In addition, it has been suggested that amyloid beta pathology is not directly linked to neurodegeneration but is rather a byproduct of amyloid precursor protein malfunction. Immunotherapies targeting tau have gained increased attention and are proving to be one of the most promising areas of research.
Tau-targeted immunotherapy currently shows the most promise as a therapeutic approach for tauopathies such as FTD. Tau oligomers have been shown to be neurotoxic, both extracellularly and intracellularly. Tau pathology correlates strongly with the stage of neurodegeneration/dementia progression and more recently, misfolded forms of tau have been shown to seed normal forms of tau and propagate cell to cell [BITTAR]. In addition, tau has been found to be a microtubule binding protein directly involved in cellular integrity which speaks to the likelihood that tau malfunction is causally linked to neurodegeneration.
CHRONIC TRAUMATIC ENCEPHALOPATHY
The neuropathology of chronic traumatic encephalopathy (CTE) is characterized by abnormal aggregations of tau proteins in the neocortex with an organized filament structure comprised of three-repeat and four-repeat tau. This organized filament structure is found only in CTE and not in other tauopathies such as Alzheimer’s Disease or Frontotemporal Dementia. Our hypothesis is that disrupting the formation of the organized filament structure through the selective removal of three-repeat tau will play a critical role in modifying the disease course of CTE.