No abstract

The amyloid-␤ peptide (A␤) deposited in plaques in Alzheimer's disease has been shown to cause degeneration of neurons in experimental paradigms in vivo and in vitro. However, it has been difficult to convincingly demonstrate toxicity of native amyloid deposits in the aged and Alzheimer brains. Here we provide evidence that the fibrillar conformation of A␤ (fA␤) deposited in compact plaques is associated with the pathologies observed in Alzheimer brains. fA␤ containing compact but not diffuse plaques in the aged rhesus cortex contained activated microglia and clusters of phosphorylated tau-positive swollen neurites. Scholl's quantitative analysis revealed that the area adjacent to fA␤, containing compact but not diffuse plaques in aged rhesus, aged human, and Alzheimer's disease cortex, displays significant loss of neurons and small but statistically significant reduction in the density of cholinergic axons. These observations suggest that fA␤ toxicity may not be restricted to cultured cells and animal injection models. Rather, fA␤ deposited in native compact plaques in aged and AD brains may exert selective toxic effects on its surrounding neural environment.

Subependymal giant cell astrocytoma (SEGCA) is a benign, slow-growing glial tumor that manifests with signs and symptoms of obstructive hydrocephalus most often in adolescent patients with tuberous sclerosis complex (TSC). Neonatal highly aggressive SEGCA is very rare. We report a 5-month-old child with TSC presenting with a cystic mass lesion in the left frontal lobe as well as multiple other periventricular masses. After initial conservative treatment, the child was readmitted with intractable seizures, a massive increase in the size of the left frontal lobe tumor and obstructive hydrocephalus. Despite surgical interventions, the child succumbed to the intracranial lesions. In this report, we discuss the challenges of managing SEGCA and the importance of further studies, including genetic studies, that may lead to a better understanding of its pathophysiology.