The possible place of cathepsins and cystatins in the puzzle of Alzheimer disease: a review.

Lysosomal proteinases (cathepsins) and their endogenous inhibitors (cystatins) have been found to be closely associated with senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles in Alzheimer disease (AD). Further, profound changes in the lysosomal system seem to be an early event in "at-risk" neurons of AD brains. There is an ongoing controversy as to whether lysosome-associated proteolytic mechanisms are causally related to the development and/or further progression of the disease. The present article deals with some arguments "pro" and "contra" an involvement of the endosomal/lysosomal pathway in amyloidogenesis as a cardinal process in AD. Other putative targets of acidic proteinases and their natural inhibitors in the pathogenesis of AD (such as formation of neurofibrillary tangles and regulation of apolipoprotein E) are also discussed.

[Quantitative cytoarchitecture point differences in experimental cortical hemiatrophy found by automatic image analysis]. / Quantitative Erfassung zytoarchitektonischer Seitendifferenzen durch automatische Bildverarbeitung am Beispiel einer experimentellen kortikalen Hemiatrophie.

For more than ten years automatic analysis procedures have been applied to explore cortical cytoarchitectonics of the brain. The investigations presented were carried out by a method described as "automatic morphocorticography". Attempts to find out quantitative criteria for early unilateral cortical alterations were carried out on a pig's brain with experimental cortical hemiatrophy caused artificially by wide spread meningeal fibrosis. Lateral differences of the relative volume density (V alpha) of all cells could be analysed for each cortical layer in detail by the automatically plotted morphocorticographs (MCG) of selected cortical parts from both hemispheres. Partial increases in the V alpha-values could be found in the whole cross-section of the cerebral cortex from the experimentally damaged hemisphere and the same value increases of between 10 and 15% were found in the 3rd an 5th cortical layer in particular. In contrast the mean values of the relative numerical cellular density in the whole cortical cross-section remained without significant changes. It can be concluded that the early alterations caused by this type of damage are predominantly due to changes in the neuropil structures.

[The effect of large-faced cerebral meningeal fibroses on the development of hemispheric volume. Experimental and morphometric studies of swine brains]. / Einfluss grossflächiger Hirnhautfibrosen auf die Entwicklung des Hemisphärenvolumens. Experimentelle und morphometrische Untersuchungen an Schweinegehirnen.

Alterations that occurred to the hemispheric structure as a result of experimentally induced meningeal fibrosis are reported in this paper. The rinsing function of cerebrospinal fluid was unilaterally stopped in the subarachnoidal space of domestic pigs by means of a viscous medium which contained soluble fatty acid salts. The animals were sacrificed 35 or 95 d after the experiments. Series of frontal sections of both cerebral hemispheres were planimetrically measured to establish differences between hemispheric cross-sections. Left-side deficits between 6 and 29% were recordable from all cases. Microscopic findings included large meningeal fibroses without visible changes to the cortex and others with destruction of cortical regions. Early alterations to cortical cytoarchitecture were investigated by means of automatic image analysis. Increased cell volume densities were recorded from the third and fifth cortical layers in cortex parts with no grossly visible alterations. The authors feel that the above alterations were primarily attributable to gradual occlusion of the lesser meningeal and cortical veins.

[Structural changes in the peripheral nerves over a lifetime. Morphometric studies of the sciatic and sural nerves]. / Lebensgeschichtlicher Strukturwandel peripherer Nerven. Morphometrische Untersuchungen am Nervus ischiadicus und Nervus suralis.

Investigations were conducted on topographically identical tissue samples from the sciatic and sural nerves. 22 autopsies on individuals free of any severe disorder provided the material for this study (stillborn babies and deaths of unnatural causes). The material was selected with the view to having all age groups of human life represented. preferably two or more subjects of each decade. The overall cross-section and the cross-section of each bundle were planimetrically measured, using magnified photographs of celloidin sections, 30 micron in thickness. Depending on age, the sum of the cross-sections of all bundles was found to percentually decrease by about one fifth in all nerves relative to the overall cross-section. Alterations in the sural nerve and in the smaller portion of the sciatic nerve (N. peronaeus communis) were characterised by linear regression of measurements with a negative correlation, but non-linear regression could be estimated for the larger portion (N. tibialis). Semi-thin sections of methacrylate-embedded material were used to ascertain the numerical density of Schwann cell nuclei on all cases and to study fibre calibre distribution on three selected subjects. The averaged numerical density of Schwann cell nuclei decreased by about 80% from birth to the age of five years and varied between the second and fifth decades within a relatively small range described by a hyperbolic regression. No unambiguous correlation was found to exist beyond the fifth decade.(ABSTRACT TRUNCATED AT 250 WORDS)

[Alcoholism and morphologic findings of the nervous system in autopsy cases]. / Alkoholismus und morphologische Befunde am Nervensystem bei Obduktionsfällen.

154 autopsy cases of alcoholics (120 men and 34 women) were investigated from a neuropathological viewpoint. In only 19 cases could typical diseases of the nervous system caused by alcoholism be found (Wernicke's encephalopathy, central pontine myelinolysis, Marchiafava-Bignami's disease and disorders of the peripheral nerves and muscles). In comparison liver diseases occurred almost five times more frequently in our own material. Diseases caused by alcoholism of the nervous system, the question of brain shrinkage and its partial reversibility, the up to now not completely known effects on the neurophil and cortical cytoarchitectonic are discussed according to the literature.

[Spinal epidural lipoma as a cause of paraplegia]. / Spinale epidurale Lipome als Ursache von Querschnittssyndromen.

Two cases (a 56-year-old woman and a 57-year-old man) with spinal epidural lipomas are described. In the discussion, the origin, the development and the biological valence of this spinal growth are dealt with. Besides, the age of the manifestation of the neurological symptoms, the localization, the clinical symptoms, diagnosis and differential diagnosis as well as therapy and prognosis of these tumours, which are rarely found in the spinal canal, are discussed. With the exclusion of the lipomatosis combined with lumbosacral malformations of the spinal column, the literature contains reports on about 66 cases of epidural and intradural spinal lipomas described until now.

[Development of the disease and autopsy findings in a case of malignant hemangioendothelioma of the right main bronchus (author's transl)]. / Krankheitsverlauf und pathologisch-anatomische Befunde bei einem malignen Hämangioendotheliom des rechten Hauptbronchus.

The case of a 47-years-old woman with malignant hemangioendothelioma growing from the wall of the right main bronchus is reported. Due to its endobronchial growth, the tumor had led to early obliteration of the bronchus with atelectasis of the right lung, perforated the bronchial wall and had grown up in the mediastinum to the size of 8,5 X 7 X 5 cm bounded by a wall of fibrous tissue. The development of the disease had required about 3 month only on the whole. Exstirpation of the tumour had not been advisable owing to its unfavourable location. In spite of the considerable size of the tumour, no metastases have been founded in the autopsy.