Six sporadic cases of dementia with lobar atrophy and neuronal cytoplasmic inclusions (Pick's disease) could be separated into two groups on the basis of the involvement of subcortical structures, the distribution and the histochemical, immunochemical, and ultrastructural characteristics of the inclusions, and possibly the age at onset. The first group (classic) was characterized by predominantly cortical atrophy and the presence in the hippocampus and neocortex of argyrophilic cytoplasmic inclusion bodies that reacted with a monoclonal antibody against neurofilament proteins and antitubulin antisera. Ultrastructurally the bodies were composed of straight fibrils of variable diameter, averaging 15 nm, and long-period constricted fibrils. The second group (generalized) showed subcortical as well as antibodies against neurofilaments and microtubules. Ultrastructurally the straight fibrils composing the bodies were coated with granular material, presumed to be derived from ribosomes. The generalized cases occurred in younger patients than did the classic cases in this series.

We studied the clinical and pathologic features of two cases of neuronal intranuclear hyaline inclusion disease. The cases were unique in late onset, presentation with dementia, possible autosomal dominant pattern of inheritance (in one patient), predominance of inclusions in glial cells, and mineral deposits within some inclusions. Differences from other reported cases indicate that this is probably not a homogeneous entity.

The technique of organotypic tissue culture offers an opportunity to observe in vitro complex interactions among glial cells and neurons, leading to the formation of myelin. In the present and accompanying work a combined ultrastructural, immunocytochemical and autoradiographic approach was used in a detailed study of the process of gliogenesis. Using immunocytochemical and ultrastructural criteria, differentiation along the oligodendroglia cell line is seen to be initiated a few days later than along the astroglial line. The sequence and timing of oligodendroglial differentiation both ultrastructurally and chemically follow those described in vivo. Formation of myelin has been demonstrated only by oligodendrocytes in which there is continuity between the perikaryal plasmalemma and myelin membranes. Oligodendroglial maturation culminated with the formation of light, medium and dark oligodendrocytes. The periodic acid Schiff-positive, glial fibrillary acidic protein (GFAP)-negative process of radial glial cells at explantation become GFAP-positive within 3 days, as described in vivo. Many of the astrocytes appear to have been derived from radial glial cells. Large numbers of dark glial cells, similar to the so-called 'intermediate glial cells', were seen. These were found to be astrocytes whose appearance probably reflected reaction to explantation-induced injury.

Exposure of the central nervous system (CNS) of rabbits to aluminum salts produces a progressive encephalopathy. Examination of CNS structures discloses widespread perikaryal neurofibrillary tangle (NFTs) formation. The aluminum-induced NFTs consist of collections of normal neurofilaments, and differ ultrastructurally and in their solubility characteristics from Alzheimer-type NFTs, the latter being composed of largely insoluble paired helical filaments. The present study compares NFTs found in the rabbit to those of Alzheimer's disease, using monoclonal antibodies (SMI 31, SMI 32) that recognize phosphorylated and non-phosphorylated determinants respectively in normal neurofilaments, and an antiserum raised against purified microtubules. Paraffin-embedded sections were stained by the avidin-biotin immunocytochemical method. Intense staining of aluminum-induced NFTs was found after processing with SMI 31 and SMI 32, while no staining of non-tangled perikarya of control rabbits or of Alzheimer-type NFTs was seen. Antimicrotubule anti-serum gave weak, nonfocal staining in the aluminum-treated and control rabbits, while Alzheimer-type NFTs were stained intensely. These results show that phosphorylated and non-phosphorylated neurofilaments accumulate in aluminum-induced NFTs, thus complementing the previously demonstrated specific slowing of the axonal transport of neurofilaments in aluminum intoxication. Further, they suggest that the presence of microtubular proteins may be necessary for altered neurofilaments to take on a paired helical configuration.

The brains of most demented patients show at autopsy the lesions of Alzheimer's disease (AD). However, the brains of other demented patients show either no morphological changes or lesions distinct from those of AD. We report clinicopathological studies on two diseases in this latter group. The study of these diseases can improve our understanding of AD.Pick's disease is characterized by dementia, lobar cerebral atrophy, and neuronal cytoplasmic inclusions. Most cases, which we have called "classical", show inclusions made up of straight fibrils that are immunologically cross-reactive with the paired helical filaments of AD. In other "generalized" cases, similar fibrils are coated by granular material and are less reactive with anticytoskeletal antibodies.In contrast to the cytoplasmic localization of the lesions in Pick's disease, it is the cell nucleus that shows abnormalities in neuronal intranuclear hyaline inclusion disease. This disease can present clinically as dementia of adult onset. Thus, either nuclear or cytoplasmic lesions can produce a pattern of neuronal dysfunction resulting in dementia. RESUME: Etudes clinicopathologiques de certaines maladies de type non-Alzheimer occasionnant de la demence. Le cerveau de la plupart des patients dements presente des lesions caracteristiques de la maladie d'Alzheimer (MA) a 1'autopsie. Cependant, le cerveau d'autres patients dements ne presente pas de changement morphologique ou presente des lesions differentes de celles de la MA. Nous rapportons des etudes clinicopathologiques au sujet de deux maladies de cette derniere categoric L'etude de ces maladies peut ameliorer notre comprehension de la MA.La maladie de Pick est caracterisee par de la demence, de l'atrophie au niveau des lobes cerebraux et des inclusions cytoplasmiques dans les neurones. La plupart des cas que nous avons designes comme ' 'classiques", comportent des inclusions constitutes de filaments droits qui presentent une reaction immunologique croisee avec les filaments helioci'des groupes par paires. Chez d'autres cas "generalises", des fibrilles analogues sont enduites d'une matiere granulaire et reagissent moins en presence d'anticorps diriges contre le squelette cellulaire.Contrairement a ce qui se passe dans la maladie de Pick ou les lesions sont localisees au niveau du cytoplasme, ce sont les noyaux cellulaires qui sont anormaux dans la maladie comportant des inclusions hyalines intranucleaires dans les neurones. Cette maladie peut se presenter comme une demence survenant a l'age adulte. Ainsi, soit les lesions nucleaires ou cytoplasmiques peuvent produire un pattern de dysfonction neuronale conduisant a la demence.

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