Search

BACKGROUND: Three major causative genes have been implicated as the cause of early-onset familial Alzheimer's disease (AD): the amyloid precursor protein gene (APP), presenilin-1 (PSEN1) and PSEN2. Although rare, a tau-related dementia with mutations in the microtubule-associated protein tau gene (MAPT) has been identified in patients showing clinical presentations similar to those of AD. METHODS: We performed mutational analysis of APP, PSEN1, PSEN2, and MAPT in 10 Japanese families with early-onset dementia clinically diagnosed as probable Alzheimer's disease. RESULTS: In 4 index patients, we identified 4 missense PSEN1 mutations, namely, L286V, G378E, L381V, and L392V. The mean age at onset in the patients with PSEN1 mutations was 39 years. In 2 families, we found the R406W mutation in MAPT. The mean age at onset of the patients carrying the R406W mutation was 52 years, and they presented with the peculiar AD-like phenotype without apparent behavioral or language problems. CONCLUSION: These observations suggest that although PSEN1 mutations are the most frequent cause, the MAPT R406W mutation is an important cause of early-onset familial dementia clinically diagnosed as AD. Differentiation of patients with the MAPT mutation from AD patients by genetic testing would be meaningful, considering that a different therapeutic approach should be applied. [ABSTRACT FROM AUTHOR]

Glucagonomas are relatively rare, and can be difficult to differentiate from other pancreatic tumors. A 62-year-old woman who had suffered from diabetes mellitus was hospitalized for further evaluation of a space-occupying lesion in the head of the pancreas and tumors in the liver. F-18 fluorodeoxyglucose positron emission tomography revealed accumulation of isotope corresponding to a tumor of the pancreas with a standardized uptake value of 4.3, and tumors in the liver with standardized uptake values of 2.4 and 2.8. The serum glucagon level was high (1,170 pg/ml) and the secretin tolerance test was negative. She was diagnosed with glucagonoma with a high serum glucagon level and clinical findings. It is suggested that glucagonoma may be one of the tumors which show high uptake of F-18 fluorodeoxyglucose. [ABSTRACT FROM AUTHOR]

Lectin cytochemistry of normal rat central nervous system (CNS) was performed on formalin-fixed, paraffin-embedded sections by using 14 lectins and light and electron microscopy. Hippocampal neurons reacted positively with Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I), Griffonia (Bandeiraea) simplicifolia lectin II (GSL-II) and Vicia villosa agglutinin (VVA); neurons in the cornu ammonis (CA) 2 region reacted positively with GSL-I and GSL-II, and neurons in the CA2 and CA3 regions reacted with VVA. Cortical neurons reacted positively with GSL-I and VVA. Cerebellar Purkinje cells and granule cells were reactive with Phaseolus vulgaris leukoagglutinin (PHA-L). Cerebellar nucleus neurons were also reactive with PHA-L and VVA. Reactivity with GSL-I, GSL-II, VVA and PHA-L was observed only on the neuronal cell surface. The present findings demonstrate the differences between cerebral and cerebellar neurons in reacting with glycoconjugates. [ABSTRACT FROM AUTHOR]

An autopsied case of postencephalitic parkinsonism of von Economo type with a 71-year duration is reported. Several cases of postencephalitic parkinsonism of von Economo type have been reported in Japan but this is the first reported case from western Japan. The patient was a Japanese man who was 74 years of age at the time of death. He developed encephalitis of unknown etiology at the age of 3 years. The first symptom was antisocial behavior, which developed at 30 years of age. At the age of 40 years, the patient showed progressive parkinsonism. Neuropathological findings disclosed marked neuronal loss with gliosis in the substantia nigra, locus ceruleus, and raphe nuclei, as well as the appearance of neurofibrillary tangles in the aforementioned areas. There were also widespread tuft-shaped astrocytes (Tu-SA) in the central nervous system, including the thalamus. Tuft-shaped astrocytes are considered to represent non-reactive astrocytes because the distributions of neurofibrillary tangles (NFT) and Tu-SA are clearly different. Therefore, the primary astrocytic lesions in postencephalitic parkinsonism of von Economo type may be more widespread. Ultrastructurally, the Tu-SA consisted of straight filaments, 15 nm in width, which formed tight bundles. Ultrastructurally, NFT in this case revealed paired helical filaments but straight filaments, 15 nm in width, which were also found in the neurons of the substantia nigra. [ABSTRACT FROM AUTHOR]

The status of Pick’s disease within the concept of frontotemporal dementia (FTD) is unclear. Some researchers have defined Pick’s disease as FTD with Pick bodies. Alternatively, the confusion may be clarified by using the term Pick body dementia (PBD) rather than by using the term Pick’s disease in a narrow sense. Pick body dementia is characterized by a prominent frontotemporal lobar atrophy, gliosis, severe neuronal loss, ballooned neurons, and the presence of neuronal inclusions called Pick bodies. In recent years, studies of Pick body dementia have advanced from the standpoint of the tau pathology. Tau-positive glial inclusions as well as neuronal inclusions have been observed in PBD and its related disorders. Various forms of FTD have been proposed based on the presence of neuronal or glial inclusions. We propose a new variant of FTD termed ‘glial tangle-predominant type’. More research is required to understand the tau abnormalities in the various forms of FTD. [ABSTRACT FROM AUTHOR]