This is an interesting study. Suo et al. propose a concept of "threshold" of Aβ in AD brain. There have been extensive studies on Aβ loads and correlation of cognitive decline. It is now clear that when so-called "subthreshold" levels of Aβ accumulate in the brain, they definitely do something, as the authors reported, i.e., sensitize microglia. More importantly, the authors claim that these subthreshold levels of Aβ may occur as oligomers. Glabe et
al. (see ARF related news story
and Walsh et al. (see ARF related news story
have reported that oligomers of Aβ may be critical in causing neurodegeneration. Thus, neuron death probably has already occurred in AD brains at a very early stage, when clinical
symptoms cannot yet be observed.
Finding that low doses of Aβ cannot stimulate TNFα release from mouse microglia is interesting. We previously reported that Aβ can directly stimulate release of TNFα and other cytokines from microglia derived from rapidly...