They have intervened late, months after the initial development of cognitive deficits. In using transgenic wild-type presenelin, they may have added early lysosomal deficits similar to human AD which impair the normal autophagic clearance of wild-type and pathological tau species.
For the first time, the model exhibits cognitive deficits that are both secondary to the accumulation of pathological tau species, and (to use a slight oxymoron) "clean," being unconfounded with the motion disorders that constituted a significant caveat to the relevance of previous models. And the vaccine has not only elicited a robust immunological response, and cleared pathological tau species from brain regions of relevance to human disease, but have linked such clearance to improved cognitive function on several extensively-used tests.
Vaccination with human phosphorylated tau led to the clearance of tau pathology from the brains of immunized mice, as revealed using both immunohistochemical staining with antibodies to the phosphorylated tau species PHF1 and AT8, and Western blot analysis of total and phosphorylated tau species (normalized with actin and total tau levels), evaluated using (respectively) polyclonal B19 antibody, and with monoclonal antibodies to PHF1 and CP13.
The new work is strong support for the therapeutic importance and tractability of the removal of pathological tau species from the brain -- in Alzheimer's disease, in other tauopathies, and in the "normal" degeneration of the aging brain. And it is yet another in a mounting series of reports offering support for the therapeutic heuristic of removing the damage of aging, to effect the rejuvenation of the body -- and the mind that coincides with its structural and functional integrity.
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