Primary cerebral venous thrombosis has a wide clinical and pathological spectrum, which has not been recognized. Seven cases of aseptic cerebral venous thrombosis (5 fatal) are discussed, with pathological study and literature review. Five patients ranged in age from 22 to 31 years. In 3 cases no discernible cause for thrombosis was found. Novel features of these cases include: primary bilateral internal cerebral venous thrombosis; isolated thrombocytopenia; occurrence in the context of (1) ulcerative colitis plus oral contraceptive use, (2) a twin transfusion syndrome, and (3) presenting syndrome five years after mastectomy for carcinoma. Diagnosis and treatment are discussed, and it is suggested that a focal coagulopathy may be responsible for this underdiagnosed condition.

We have isolated a novel Alu sequence-containing cDNA, designated AD7c-NTP, that is expressed in neurons, and overexpressed in brains with Alzheimer's disease (AD). The 1,442-nucleotide AD7c-NTP cDNA encodes an approximately 41-kD protein. Expression of AD7c-NTP was confirmed by nucleic acid sequencing of reverse transcriptase PCR products isolated from brain. AD7c-NTP cDNA probes hybridized with 1. 4 kB mRNA transcripts by Northern blot analysis, and monoclonal antibodies generated with the recombinant protein were immunoreactive with approximately 41-45-kD and approximately 18-21-kD molecules by Western blot analysis. In situ hybridization and immunostaining studies localized AD7c-NTP gene expression in neurons. Using a quantitative enzyme-linked sandwich immunoassay (Ghanbari, K., I. Beheshti, and H. Ghanbari, manuscript submitted for publication) constructed with antibodies to the recombinant protein, AD7c-NTP levels were measured under code in 323 clinical and postmortem cerebrospinal fluid (CSF) samples from AD, age-matched control, Parkinson's disease, and neurological disease control patients. The molecular mass of the AD7c-NTP detected in CSF was approximately 41 kD. In postmortem CSF, the mean concentration of AD7c-NTP in cases of definite AD (9.2+/-8.2 ng/ml) was higher than in the aged control group (1.6+/-0.9; P < 0.0001). In CSF samples from individuals with early possible or probable AD, the mean concentration of AD7c-NTP (4.6+/-3.4) was also elevated relative to the levels in CSF from age-matched (1.2+/-0.7) and neurological disease (1.0+/-0.9) controls, and ambulatory patients with Parkinson's disease (1.8+/-1.1) (all P < 0.001). CSF levels of AD7c-NTP were correlated with Blessed dementia scale scores (r = 0. 66; P = 0.0001) rather than age (r = -0.06; P > 0.1). In vitro studies demonstrated that overexpression of AD7c-NTP in transfected neuronal cells promotes neuritic sprouting and cell death, the two principal neuroanatomical lesions correlated with dementia in AD. The results suggest that abnormal AD7c-NTP expression is associated with AD neurodegeneration, and during the early stages of disease, CSF levels correlate with the severity of dementia.

No abstract

No abstract

AD7C-NTP (neural thread protein) is a approximately 41-kD brain protein that is selectively elevated in Alzheimer disease (AD). AD7C-NTP is associated with the pathologic changes of AD, and overexpression of the AD7C-NTP gene is associated with cell death similar to that found in the AD brain. A newly developed competitive ELISA (enzyme-linked immunosorbent assay) was tested in urine samples from patients with AD, patients with non-AD dementia, and healthy normal individuals. Mean assay measurement in the AD group (30.1 +/- 10.8) was significantly higher than in the non-AD dementia control group (13.4 +/- 3.4) and in the nondementia control group (14.8 +/- 5.2) (P <.001). Mean assay measurement in early-AD cases (25.3 +/- 7.6) was significantly lower than in other AD cases (33.9 +/- 11.4). Levels of more than 18 units were found in 89% of overall AD cases and in 10% of overall controls. The results further validate urinary AD7C-NTP as a biochemical marker for AD and indicate that the competitive ELISA-format AD7C-NTP test in urine is an accurate method for determining AD7C-NTP levels in AD.