Bruce Yankner took time out from his talk on Down's syndrome (Abstract 7) to discuss his recent injection studies in young versus aged rhesus monkeys, published in the July issue of Nature Medicine. His key findings were that injections of fibrillar Aβ at a "plaque equivalent dose" resulted in cell loss, the proliferation of microglia and tau hyperphosphorylation in aged animals, but not young ones. These findings are in contrast to earlier studies by Podlisny and Selkoe (where "adult" but not "aged" monkeys were used).
Yankner showed an interesting example of immunocytochemical staining for Aβ revealing an "injected plaque" near a natural plaque in an aged monkey. The injected Aβ was more lightly stained and diffuse than the natural plaque, and was oblong in shape, as if oriented along the needle tract. Without the natural plaque present for comparison, one would have assumed the artificial plaque was real based on morphology. Yankner used several antibodies to hyperphosphorylated tau, including Ser-262, PHF-1 and AT8 to demonstrate dystrophic neurites in response to the injection. He indicated that Ser-262 yielded the strongest staining, with PHF-1 next and weak staining by AT8. This reaction was not seen in the brains of young rhesus monkeys. In the brief time allotted, he was unable to show slides of vehicle injections in neither aged monkeys nor Aβ injections in young monkeys for the audience to evaluate. Given Selkoe's observations that the neuropil response to vehicle injections was indistinguishable from Aβ injections and Bishop et al's poster (Abstract 535) which shows that there is neuronal damage and loss surrounding saline control injections into rat brain this is an important question. The curious will have to examine Yankner's Nature Medicine paper for the details.
Yankner favors the position that extracellular Aβ is the bad guy compared to intracellular Aβ, pointing out that the intracellular Aβ "load" is "minuscule" compared to the extracellular "load." Thus, the toxic effects of extracellular Aβ are probably more important. He hypothesizes that intracellular Aβ from a cell which lyses could lead to a seeding process which accumulates extracellular Aβ, propagating the problem.—Brian Cummings
No Available References
No Available Further Reading