PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis.

The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4'-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-epsilon4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Abeta) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Abeta-peptide related cerebral amyloidosis.

Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.

The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex.

An animal model of prophylactic cranial irradiation: histologic effects at acute, early and delayed stages.

Wistar rats (body wt. 200 g) were subjected to a fractionated course of radiation similar to that used in prophylactic brain irradiation for small cell carcinoma of the lung (2000 cGy in 5 fractions over 5 days with 60Co). Effects of this regimen were assessed by histologic examination of brain sections at 1 week, 1 month and 6 months post-irradiation. With conventional stains there were no apparent differences between control and irradiated brains at any of the post-irradiation intervals. Immunohistochemistry for neurotransmitter synthetic enzymes tyrosine hydroxylase and glutamate decarboxylase, as well as histochemistry for acetylcholinesterase, failed to uncover any changes in the irradiated animals. Immunohistochemistry for glial fibrillary acidic protein, an astrocyte marker, also showed no differences in the irradiated groups. However, an antibody against a major histocompatibility complex, class II antigen (OX-6) revealed a microglial response in grey and white matter beginning at 1 month and increasing up to the 6 month post-irradiation interval. The neuroanatomical basis for this microglial response was suggested by the results of silver stains for nerve axons, which revealed axonal loss in striatal white matter bundles in a pattern implicating vascular insufficiency.