With Aβ, the danger lies within

The most obvious symptom is not always the most relevant. In Alzheimer's disease (AD), for example, post-mortem brain analyses show large extracellular amyloid plaques of fibrillar Aβ protein. But the plaques arise late, whereas an intracellular version of the toxic protein fragment (Aβ_1–42, a fragment of the amyloid precursor protein) is seen earlier, coincident with the first cognitive defects. Now Zhang et al. (page 519) show that minute amounts of this intracellular Aβ_1–42 are toxic to primary neurons, even when injected directly into the cytoplasm.The final concentration of injected Aβ_1–42 is 1–100 pM, for a total of somewhere between 1,500 and 150,000 molecules per neuron. In contrast, the same neurons are not significantly affected by up to 10 μM extracellular Aβ_1–42, nor by intracellular...