What mediates between beta-amyloid and paired helical filaments?

beta-Amyloid precedes helical filaments (PHF), and both appear to be relatively independent alterations, contrary to the previous view. One of the mediators between beta-amyloid and PHF should be a trophic factor(s). Unbalanced trophic activities in the AD brain result in massive sprouting of vulnerable neurons, leading to their exhaustion and death.