Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered as a new disease predominantly affecting the small vessels of the brain with an autosomal dominant transmission linked to chromosome 19. This review includes an historical perspective showing how the disease was identified from the spectrum of vascular leukoencephalopathies. More than two hundred patients have now been described, belonging to at least 30 unrelated pedigrees in Europe, America and Asia. The clinical features include four major neurological presentations associated in variable degrees during the course of the disease: migraine with or without aura, strokes or stroke-like episodes, major psychiatric symptoms and dementia. The patients are free of the classical vascular risk factors. The disease has a progressive or stepwise course with age at onset in the forties and a mean duration of 13.6 +/- 10.7 years. Death occurs in the fifties in a characteristic condition associating a pseudo-bulbar syndrome and subcortical dementia. Cerebral magnetic resonance imaging (MRI) is highly contributive to the diagnosis, showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter. Pathological data show macroscopic lesions similar to Binswanger's disease but different lesions of the small vessels including thickening of the media, characteristic PAS+ granular material and narrowing of the lumen. Skin biopsy may be a valuable diagnostic tool, showing ultrastructural alterations of skin vessels similar to those of brain vessels. The disease is highly homogeneous on a genetic basis and the identification of the gene Notch 3 on chromosome 19 has opened new avenues for research and genetic counselling. The pathogenesis of the disease has still to be elucidated. A definite diagnosis relies on genetical or pathological data. Diagnostic criteria are proposed to recognize the disease on clinical and imaging parameters. So far, no treatment has been reported to be successful for CADASIL. Copyright Lippincott-Raven Publishers
Senile plaques (SP) are one of the neuropathological hallmarks of senile dementia of the Alzheimer type (SDAT). In 14 patients affected with SDAT (over 74 years of age), thioflavine S, Tau and acetylcholinesterase (AChE) stainings demonstrated an increased density of SP in the outer two thirds of the dentate gyrus molecular layer. However, a wide range of SP density was observed among the cases. The molecular layer of the dentate gyrus is one of the termination site of the perforant pathway that originates in layers II and III of the entorhinal cortex. We have found that the number of AChE-, thioflavine S- and Tau-positive SP that accumulate in the dentate gyrus is positively correlated with the density of thioflavine S-stained neurofibrillary tangles in layers II and III of the entorhinal cortex. In contrast, a similar correlation is not found when using Tau immunolabeling of the entorhinal tangles. These observations show an association between the accumulation of AChE-positive SP in the dentate molecular layer and the lesions of the perforant pathway. Furthermore, they suggest that the density of SP in the dentate gyrus correlates with the late stages of neurofibrillary tangles formation (thioflavine S positive), but not with the early stages (Tau positive).
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