Figure 1.

Intraneuronal Aβ42 accumulation occurs in AD-vulnerable neurons before the formation of senile plaques. A, Left: Neuronal Aβ42 staining (RU antibody) in the CA1 region of hippocampus derived from a 64-year-old patient with mild (CDR 0.5) cognitive dysfunction. Right: Aβ40 staining from the same CA1 region shows only slight immunoreactivity compared with the more pronounced intracytoplasmic staining seen with Aβ42. Antibody concentrations and time of development were equivalent. Bar = 60 μm. B, Left: Aβ42 immunoreactivity (RU antibody) in basal forebrain magnocellular neurons. Right: This staining is abolished by Aβ1–42 peptide competition; a blue filter was used to highlight negatively staining neurons. Bar = 60 μm. C, Left: Aβ42 staining (QCB) in the CA4 region of hippocampus from a neurologically normal 3-year-old patient (control); only faint neuronal staining can be seen (left), Bar = 60 μm. Center: Pronounced CA4 Aβ42 immunoreactivity (QCB) in a 3-year-old with Down’s syndrome. The arrow indicates a neuron with intracellular staining. Bar = 40 μm. Right: Aβ42 staining (QCB) in a 79-year-old without dementia indicates marked Aβ42 intracellular staining in layer II neurons (arrows) of the entorhinal cortex. Bar = 100 μm. D, Left: In this 83-year-old cognitively impaired subject (CDR1), the absence of intranuclear Aβ42 staining is evident in neurons stained for Aβ42 (RU). Early Aβ42 aggregates appear to be present within a neuron marked by an arrow; the inset provides another example of such seemingly intracellular Aβ42 accumulation in (RU) in a 94-year-old CDR 2 case. Bar = 40 μm. Center: “Neuronal” shaped SP (arrow) adjacent to a more conventional spherical SP in a 72-year-old subject with advanced AD (RU Aβ42). Bar = 60 μm. Right: The CA1 region of a 79-year-old cognitively impaired subject (CDR1) demonstrates both intraneuronal Aβ42 immunoreactivity (QCB) and apparent extraneuronal diffuse plaque-like staining (arrow) adjacent to a few neurons. Bar = 40 μm.