Enhanced intraneuronal accumulation of amino-terminally truncated Aβ in autism.

Mapping of Aβ_17–24 in the brain AN09402 reveals brain region– and cell type–specific patterns of abnormal Aβ accumulation in the cytoplasm of neurons and glial cells of a male diagnosed with dup(15), autism and intractable epilepsy, whose sudden unexpected death at the age of 11 years was seizure-related. Almost all neurons in the frontal (FC) and temporal cortex (TC) are 4G8-positive, but the reaction intensity varies from weak to strong. Strong immunoreactivity is observed in many neurons in the lateral geniculate body (LGB), thalamus (Th), amygdala (Amy), Purkinje neurons and basket and stellate neurons in the molecular layer in the cerebellar (Crb) cortex, in many neurons and astrocytes in the CA4, and large and small neurons in the dentate nucleus (DN). Some types of neurons (in the reticular nucleus in the thalamus and small neurons in the dentate nucleus) have different types of deposits: fine-granular and 2- to 3-µm in diameter 4G8-positive deposits. No reaction or only traces of a reaction detected with mAb 6E10 in the frontal cortex, thalamus, cerebellum and dentate nucleus indicate that in intraneuronal Aβ the amino-terminal portion is missing, and the prevalent form of Aβ is α-secretase product. Immunoreactivity with mAb 4G8 is present in the brain of the control subject (14 years of age), but fewer neurons are positive, and immunoreactivity in the frontal cortex, thalamus, cerebellum and dentate nucleus is weaker than in the affected subject. In the control subject, glial cells are usually 4G8-immunonegative.