Search

Immunohistochemistry with antisera against tyrosine hydroxylase was performed on neurons with Alzheimer's neurofibrillary changes in the substantia nigra and locus ceruleus. These specimens were obtained from brains with Alzheimer's disease, Pick's disease, progressive supranuclear palsy, Alzheimer's type parkinsonism, parkinsonism-dementia complex on Guam, and normal aging. Under these neurologic conditions the affected catecholamine neurons with Alzheimer's neurofibrillary changes were stained positively with antisera against tyrosine hydroxylase. The results suggested that in these neurons, Alzheimer's neurofibrillary changes seemed to develop independently before the reduction of tyrosine hydroxylase protein synthesis.

This paper describes the isolation and partial purification of the straight fibrils that occur in the neurons of Pick's disease. Pick fibrils are highly insoluble in a variety of solvents. These fibrils were shown to be sodium dodecyl sulfate insoluble even in the presence of a reducing agent at elevated temperatures. This allowed the selective isolation of the fibrils using the SDS boiling procedure and sucrose gradient centrifugation that have been described for isolation of paired helical filaments of Alzheimer's disease. The isolated fibrils retained the native morphology seen in tissue sections, but some appeared to become unraveled to yield a paired helical appearance. These results indicate that the Pick fibrils have many chemical and structural characteristics in common with Alzheimer paired helical filaments, and suggest that these two diseases may be closely related.

One hundred brains of patients with Down's syndrome (DS) who died in institutions for chronic care were examined for clinicopathological correlation of Alzheimer's disease. Fifty-one were below and 49 were above age 30 years at death. Tissues from the right, prefrontal, and hippocampal cortices were processed for microscopy using H&E and Bodian-periodic acid-Schiff impregnation. Morphometric evaluations of plaques and tangles were carried out. Plaques or plaques and tangles were found in the brains of 56 patients with DS, 7 below age 30 and 49 above that age. A history of dementia was evident in the medical records of 15 of these patients; of these only 2 were below the age of 30. The brains of the patients with DS who also had clinical dementia had more than twenty plaques or plaques and tangles per 1.5 X 10(6) micron 2 of cortex. The numbers of plaques and tangles found in the brains of the patients with DS above the age of 30 greatly increased with age but varied from brain to brain. These observations suggest a correlation among dementia, the density of plaques and tangles, and age. All 100 brains studied showed early arrest of brain growth and brain atrophy, a condition that may have been due to prenatal arrest of neurogenesis mainly in the granular cell layers, prenatal and postnatal arrest of synaptogenesis, and early aging. Plaques and tangles developed twenty to thirty years earlier and dementia was clinically detected at least three times more frequently (20 to 30%) in DS than it is known to occur in the non-DS population.

With neuropathological diagnosis as the point of reference, the accuracy of clinical diagnosis was studied in a series of 58 demented patients. Alzheimer's disease and multi-infarct dementia were recognised with sensitivities and specificities exceeding 70%, whereas combined dementia as a separate group was relatively unreliably diagnosed. The value of Hachinski's Ischaemic Score in differentiating between Alzheimer's disease and vascular dementias was demonstrated. Its performance was to some extent improved by assigning new weights to the items. In a logistic regression model, fluctuating course, nocturnal confusion, and focal neurological symptoms emerged as features with the best discriminating value, and helped to diagnose correctly 89% of the Alzheimer and 71% of the vascular dementia patients.

Cryostat-cut sections of formalin-fixed and unfixed hippocampus from 23 Guamanian Chamorros with clinically and neuropathologically verified amyotrophic lateral sclerosis (ALS) (8 cases) and parkinsonism-dementia (PD) (15 cases) and from 12 neurologically normal Guamanians (5 with and 7 without neurofibrillary degeneration) were evaluated by the immunoperoxidase technique, using monoclonal antibodies against phosphorylated neurofilament, human fetal microtubule-associated protein tau, and paired helical filaments. On immunostaining, all three antibodies showed intracellular tangles in the hippocampal neurons of patients with ALS, patients with PD, and in neurologically normal Guamanians with neurofibrillary pathology, but the correlation of immunostaining between these antibodies was not absolute. Extracellular or ghost tangles were immunostained only with the antibody against paired helical filaments. Our immunocytochemical data indicate that the antigenic composition of neurofibrillary tangles in Guamanian ALS and PD is similar to that of Alzheimer's disease, suggesting a common pathogenetic pathway for neurofibrillary tangle formation in these neurodegenerative disorders.

A cell-free bovine derived collagen matrix was used to study potential axonal regeneration in transected rat spinal cord. Rats were initially subjected to a 200 g/cm force acceleration injury at T10 and 10 days later, the spinal cord was totally transected at the injury site. Controls had their spinal cord stumps juxtaposed end-to-end following transection. Experimental rats had 3-4 mm of spinal cord tissue trimmed from the proximo-distal stumps. The semi-fluid collagen material was implanted to bridge the proximo-distal ends and after several hours, the collagen graft polymerized to a firm gel. Rats were observed for 90 days. After 90 days, animals were evaluated using somatosensory evoked potentials, local spinal cord blood flow, and catecholamine histofluorescence in and around the site of transection. Results suggest that the collagen bioimplant can support the development of anastomotic blood vessels with the cord as well as provide a non-hostile environment to regenerating spinal cord axons.

The presence of Lewy body and neurofibrillary tangle in the locus ceruleus neurons of aged brain is described. Ultrastructural study revealed that in some Lewy bodies the presence of "twisted tubules" or "paired helical filaments" amongst the filaments of the Lewy body. A quantitative analysis of serial sections of locus ceruleus from aged brain, incidences of the Lewy body and neurofibrillary change were 0.07% (9/11,515) and 6.6% (15/11,515), respectively. The incidence of neurons containing both structures was 0.008% (1/11,515).

Cortical biopsies were taken from the frontal lobe of 25 patients with presenile dementia. Choline acetyltransferase (ChAT) activity, and in some specimens the high affinity uptake of choline, was used to estimate loss of cholinergic nerve terminals. Of the 15 samples with varying degrees of histological evidence of Alzheimer's disease (AD) 14 were from clinically suspected examples of the disease. There was significant loss of ChAT in 10 of the 15 compared with control and the mean activity was also highly significantly reduced (to 41% of control). The deficit was found in patients examined within a year of onset of symptoms. In 6 biopsies from clinically suspected cases of AD without diagnostic histological features there was loss of activity in only one, subsequently shown to have Jakob-Creutzfeldt disease. The remaining samples were two of vascular dementia (no loss of ChAT), one probable disorder of white matter (no loss of activity) and one undiagnosed disorder (with loss of ChAT activity). Thus most patients without histologically demonstrated AD had no evidence of a presynaptic cholinergic defect. It was concluded that suspected cases of AD particularly suitable for putative cholinergic therapy were those with an onset of the disease at 55 to 65 and an absence of family history.

Young New Zealand white rabbits (1.5 kg body weight) subjected to daily subcutaneous injection of aluminum tartrate (7.7 mg/kg body weight) developed neurofibrillary tangles (NFTs) in specific areas of the central nervous system. The NFTs were initially observed in the spinal cord and brain stem. The hippocampus was the last region to show NFTs. Animals neither died nor showed any neurologic signs. Their growth pattern during and following the aluminum injection was comparable to that of controls. Energy-dispersive X-ray spectrometry detected aluminum within the nucleus of a high percentage of NFT-bearing neurons in the spinal cord and hippocampus. Aluminum was not detected in NFT-free neurons. These findings suggest the association of intranuclear aluminum with NFTs induced experimentally in the chronic animals.

Considerable controversy exists concerning the origin and composition of Alzheimer neurofibrillary tangles (ANT) and of paired helical filaments (PHF), the abnormal cytoplasmic fibers which ultrastructurally are the major components of ANT. Thus far, the unusual solubility properties of PHF have hindered the analysis of ANT. A new procedure is presented for isolating purified PHF which are soluble in the presence of sodium dodecyl sulfate. The purification protocol involves differential and rate zonal centrifugation, treatment with the detergents sarcosyl and sulfobetain 3-14, and sonication. The isolated PHF from Alzheimer disease/senile dementia of the Alzheimer type (7 cases) and Down's syndrome (one case) have been characterized structurally by negative-stain electron microscopy, biochemically by PAGE, and immunologically by both the ELISA technique and Western blot analysis using a monoclonal antibody prepared against ANT. Distinct polypeptides were shown to be associated with this structure and not seen in preparations from young and age-matched normal brains.

Results of autopsies have indicated that people with Down syndrome who live longer than 40 years develop the brain pathology of Alzheimer disease, a presenile dementia. Because of their initially low levels of mental functioning, Down syndrome persons' clinical symptoms frequently go undetected until the disease is advanced and deterioration severe. Study of this doubly inflicted population is critical to development of appropriate assessment methods and to the study of the role of genetics in aging. A preliminary investigation of the AAMD Adaptive Behavior Scale (ABS) as a potential diagnostic tool was presented. The ABS clearly differentiated the regressed from the well-functioning Down syndrome individuals, offering promise as a practical assessment device.

Thirty cases of Alzheimer's disease and 30 age-matched controls were studied to determine the incidence of cerebral amyloid angiopathy and its relationship to age, neuritic plaque formation, and amyloid plaque content. Cerebral amyloid angiopathy (CAA) was present in 86% of AD cases and 40% of age-matched controls. Its frequent occurrence in AD is not merely a reflection of the advancing age of this group: it was seen only in the presence of neuritic plaques, regardless of age, and represents an integral component of AD. Neuritic plaques however, did occur in the absence of CAA in 17% of all cases. The amount of vascular and plaque amyloid tended to be of comparable severity in many cases, but significant discrepancies were observed, with preferential deposition of amyloid in either plaque or vessel. Our results suggest that neuritic plaque formation and amyloid deposition are linked genetically or etiologically, but independently expressed, without a cause-and-effect relationship.

To study electron microscopically intracortical connections between areas 18 and 19 in the visual cortex of the cat brain, the distribution of synaptic terminals in every lamina of these areas was investigated after dissection of their border as deep as the grey matter. Mainly axo-dendritic synapses in large, small dendrites and in spines degenerated according to "light" and "dark" types were subjected to degeneration. All the laminae of the cortex were stated to participate in the formation of overlapping intracortical connections of areas 18 and 19. The greatest nember of altered synaptic buds, however, were detected in the middle layers, that correlated the data of the light optic method (A. S. Iontov, 1961, 1962). To obtain more objective data on the number of intracortical fibrils connecting these areas, normal and altered synapses up to 100 units were counted in every layer. Uneven localization of intracortical connections in every layer and their different functional importance were demonstrated.

Brain samples from cases of Alzheimer's disease, postencephalitic Parkinson's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, and Pick's disease, as well as from a case of Alzheimer's disease with a large number of Hirano bodies, were stained with the peroxidase-anti-peroxidase method using an antiserum previously shown to immunoreact with normal neurofilaments and neurofilament polypeptides. The specificity of this serum was confirmed by absorption an purified neurofilament proteins. Neurofibrillary tangles of Alzheimer's disease, postencephalitic Parkinson's disease, and progressive supranuclear palsy, Pick's bodies, and the fibrillary inclusions of amyotrophic lateral sclerosis were all immunostained. Hirano bodies showed no immunostaining. Thus, with the exception of the Hirano bodies, all the neuronal fibrillary inclusions examined appeared to share common antigenic characteristics. The orgin of all these structures from normal neurofilaments is postulated.

The severity of certain "senile" changes, namely senile plaques, neurofibrillary tangles and granulovacuolar degeneration in the neocortex and hippocampus, was estimated by light microscopy, in brains obtained at autopsy from 16 cases aged 24 to 93 years. An assessment of certain features of plaques and tangles as well as Hirano-bodies (also associated with senile change) was made by electron microscopy. A statistically significant correlation was found between the electron-microscopic and light-microscopic findings. The findings in an additional 4 cases aged 39 to 65 years in which only the cortex was examined supported the correlation.

Electron microscopic and Golgi studies on the inferior lobes of sunfish and goldfish are described. The inferior lobe consists primarily of a nucleus ventricularis of densely packed cells surrounding the lateral recess of the third ventricle, and a peripherally situated nucleus diffusus consisting mostly of scattered neurons. A cell-sparse zone of dense neuropil is located between the two cellular areas. Neurons of both nuclei have spiny dendrites and axons which originate from basal dendrites. In some cases axons are found to send a collateral into the cell-sparse zone. Neurons of the nucleus diffusus possess collaterals that extend a considerable distance within the nucleus itself. The ultrastructure of cells of both nuclei reveals cytoplasmic organelles typical of most neurons. Synapses containing dense-cored and clear vesicles are present on the spines and shafts of the dendrites of both neuronal types. In only rare cases synapses were observed on the soma of neurons of the nucleus ventricularis. Possible anatomical substrates involved in the control of feeding and aggression in teleosts are considered in light of the present findings. Morphological similarities of the inferior lobes and related areas in various fishes and amphibians are discussed and their possible significance for the understanding of the evolution of hypothalamic mechanisms is considered.

In addition to the well known structural stigmata which accompany the senile dementia of Alzheimer, attention is called to the presence of a group of robust changes which affect the fine vessels (capillaries, capillary arterioles and capillary venules), particularly of the cerebral cortex. These alterations include irregular pouches and excrescences on the vessels (a "lumpy-bumby" appearance), general thickening of the basement membrane, loss of the fine perivascular neuronal plexus which seems to invest each vessel, no matter how small, and the appearance of pits or lacunae in the vessel walls of about one half of the Alzheimer patients studied. None of these changes have been seen in a group of approximately age-matched, non-demented controls. Much of this perivascular neural plexus originates within a few specific subcortical fields, especially the locus ceruleus and the nucleus basalis of Meynert and basal forebrain area. These also happen to be included among those brain areas which experience the most marked neuronal atrophy or loss in Alzheimer's disease. Since there is some evidence suggesting that surgically induced vascular denervation in myocardium produces dramatic changes in vascular wall structure we wonder whether neuronal pathology developing initially in these subcortical areas may not play a significant role in the development of the characteristic neuropathology in Alzheimer's disease. These speculations emphasize the possible importance of a failing blood brain barrier in the development of the disease.

Microtubule associated protein tau factor self-assembles into filamentous structures resembling the paired helical filaments found in Alzheimer disease. Tau polymerization requires of a previous modification; conversion of glutamine into glutamic acid by deamination.

Most of the identified constituents of the filamentous inclusions characteristic of the neurodegenerative diseases of aging are derived from the cytoskeleton. This study was undertaken to define immunocytochemically the cytoskeletal constituents of the filamentous cytopathologic marker of idiopathic Parkinson disease, the Lewy body (LB). An array of antibodies specific to neurofilaments, tubulin, microtubule associated proteins (tau, MAP1 and MAP2) and Alzheimer neurofibrillary tangles (NFT) were used to immunostain sections containing LB. All the antibodies to tubulin, MAP1 and MAP2 and the majority of the antibodies to neurofilaments and NFT recognized LB. The two monoclonal antibodies to NFT that recognize LB also react with ubiquitin, which has been identified in NFT. The prominent NFT component, tau, is apparently not incorporated into LB. These findings suggest that the presence of tau might not be a prerequisite to the formation of abnormal filaments. Therefore, although LB contain elements of neurofilaments, microtubules and ubiquitin, as do other abnormal neuronal filaments, they are distinct in composition. These distinctive and shared features may provide useful insights regarding the mechanisms underlying the formation of filaments in LB as well as those of other neuronal inclusions.

Neurofilaments purified from invertebrate giant axons have been analyzed with the electron microscope. The neurofilaments have a helical substructure which is most easily observed when the neurofilaments are partially denatured with 0.5 M KCl or 2 M urea. When the ropelike structure comprising the neurofilaments untwists, two strands 4--5.5nm in diameter can be resolved. Upon further denaturation these strands break up into rod-shaped segments and subsequently these segments roll up into amorphous globular structures. Stained, filled densities can be resolved within the strand segments, and these resemble similar structures observed within the intact neurofilaments. The strands appear to consist of protofilaments 2--2.5 nm in diameter. These observations suggest that the neurofilament is a ropelike, helical structure composed of two strands twisted tightly around each other, and they su-port the filamentous rather than the golbular model of intermediate filament structure.

In Wistar rats the intraveneous injection of streptozotocin (65 mg/kg body weight) caused a permanent hyperglycemia. After 5 days there were lesions in the exocrine parenchyme of the pancreas and its nerve fibers. Pathological changes were found in cytoplasm, cell membrane, nucleus and all other cell organelles, too. The zymogen granules remaining after extensive degranulation may disintegrate in two different ways: 1. Shrinking of the granules and formation of a hale between granule membrane and core, the electronic density of which is decreased; indistinct demonstrability of the granule membrane and finally its decomposition. 2. Shrinking of the granules, decrease of the electron density and either homogeneous or mainly peripheral arrangement of the disintegrated material of the granules; irregular shape of the granules and splitting of their membranes.

Synapses from Mauthner to giant fibers in the hatchetfish are chemically transmitting excitatory axo-axonic synapses located in the medulla. The synapses are 4--10 mum in diameter and easily identified for electron microscopy. Presynaptic vesicles are clustered near the contact regions and are round, clear and 40-60 nm in diameter. Stimulation of the Mauthner fiber at 10/sec for 10 min greatly reduces PSP amplitude and causes profound changes in presynaptic structures. Synaptic vesicles become few in number and there is a marked accumulation of irregular membranous structures. These changes are reversible. During the recovery period, the number of synaptic vesicles progressively increases to control values, and the number of irregular membranous structures declines. Further, stimulation during cooling induces depletion of vesicles together with a great increase in the surface area of the presynaptic membrane and in the number of coated vesicles. Internal irregular membranous structures are few. Our data provide evidence for the vesicular release of transmitter and are consistent with there being a mechanism of membrane recycling in which vesicle membrane fuses with the presynaptic membrane and is reclaimed from it by coated vesicles that then coalesce to form irregular membranous structures from which new synaptic vesicles are formed.

Paired helical filaments (PHF) are neuronal landmarks of Alzheimer's disease. These pathological filaments are antigenically related to proteins present in the normal cytoskeleton, particularly to microtubule associated protein Tau. The evidence for these common epitopes was studied on sections of cortex from Alzheimer brains after Araldite embedding. Two rabbit immune sera were used: one was raised against PHF isolated from Alzheimer cortex; the other against Tau proteins extracted from bovine cortex. The comparison of adjacent semi-thin sections alternatively treated with anti-PHF and anti-Tau immune sera reveals that both stained degenerating neurofibrils in pyramidal perikarya and in neurites surrounding senile plaques. On ultra-thin sections, double immunogold labelling of PHF was obtained. These results are in accordance with the hypothesis that Tau proteins are major antigenic components of PHF.

Azzarelli et al reported an Indiana kindred affected by a hereditary disorder, characterized clinically by ataxia, parkinsonism, and dementia. Recently, we studied neuropathologically the 3rd and 4th cases that came to autopsy among the patients of this family. As in 2 patients examined previously, amyloid plaques were widespread throughout the cerebrum and the cerebellum, whereas neurofibrillary tangles were numerous in the cerebral cortex, the hippocampus, and the substantia innominata. Amyloid plaques were not recognized by polyclonal antibodies against the Alzheimer's disease amyloid A4 protein, but did contain epitopes recognized by antibodies against a prion protein. Spongiform changes were occasionally observed and were mild. Our findings indicate that this familial disorder is a form of or is related to Gerstmann-Sträussler-Scheinker disease. The consistent presence of numerous neurofibrillary tangles may be important in differentiating a distinct subgroup of patients with familial Gerstmann-Sträussler-Scheinker disease, and indicates that a disturbance of the cytoskeleton might be part of the neuronal pathology of Gerstmann-Sträussler-Scheinker disease.

The extensive cytoskeleton present in brain tissue is composed of microfilaments, neurofilaments, and neurotubules. A clear understanding of each of these structures is required to accurately define their participation in neuronal functions. Until more is known, therefore, we are restricted to speculate on their importance to the general activity of the cell. The presence of microfilamentous proteins in nerve endings -- the sites where nerve transmission is chemically sustained -- strongly suggests their participation in the release of putative neurotransmitters, a hypothesis that may be substantiated in the near future. It follows that alteration in assembly, disassembly, or interaction among the various cytoskeletal components may permit some insight into the causes and origins of a variety of neurological alterations affecting humankind.

Nerve cell nucleolar volume in reduced, in senile dementia of Alzheimer type, by 15 - 25% in nerve cells not containing neurofibrillary tangles and by over 35% in those which do contain such changes, in a wide variety of brain regions, when compared to similar cells from non-demented control cases, suggesting that interference with production of proteins may be an early consequence of the pathogenic process. The extent to which nucleolar volume is decreased in the non-tangle-bearing cells is related to frequencies of both neurofibrillary tangle and senile-plaque formation within that region, but the reduction in volume in the tangle-bearing cells correlated with neurofibrillary changes only. It seems, therefore, that the severity with which the dementing process affects an area of brain is initially shown by alterations in cell metabolism, which may invoke reductions in protein synthesis in non-tangle-bearing cells, and is later marked by the proportion of these affected cells which go to form neurofibrillary tangles. Changes in nerve cell function do not seem to be as well indicated by the density of senile plaques within that area.

A man aged 70, showed early disorientation, memory defects, delusions and rages at 66, later mental deterioration with muteness and dysphagia. He died of cardiac failure. The postmortem examination revealed macroscopically and light microscopically the neuropathological findings of atypical senile dementia. Moreover, it is the interesting characteristic in the presented case that there are electron microscopically two types of filaments making the neurofibrillary tangles. One showed the so-called "paired helical filaments", which were observed in the cerebral cortex. The other showed paralled "straight filaments". These "straight filaments" were found in the bilateral hippocampi.

Presented studies reveal that each of the approximately 10 nm filaments forming the paired helical filaments (PHF) is made up of four protofilaments. Each of the protofilaments is a beaded structure, consisting of globules connected by longitudinal bars. A cross-view of PHF shows eight globules linked by transverse bars. The transverse bars are shorter than the longitudinal bars. Comparison between PHF and neurofilament protofilaments indicates structural differences between these profiles, i.e., the globules making the PHF protofilaments are larger and the longitudinal bars are longer than those in the normal neurofilaments. A three-dimensional diagram of PHF structure is presented.

The authors present a study on ultrastructural changes observed in aged human and animal brain. These changes are analyzed and compared with those described in classic optic microscopy and with those observed in experimental models of the same lesions.

A quantitative analysis of the afferent innervation of the organ of Corti was made on normal and vestibular nerve-sectioned guinea pigs. Section of the vestibular nerve at the internal auditory meatus provided an efficient means of eliminating the efferent innervation to the cochlea without significant loss of afferent fibres. Nerve counts on normal and de-efferented animals revealed that about 10-15 % of the cochlear afferent innervation supplies the outer hair cells. The remaining 85-90% of afferent fibres innervate the inner hair cells. As in cats, all tunnel spiral bundle fibres and upper tunnel crossing fibres were efferent to outer hair cells. Since unmyelinated fibres in the osseous spiral bundle were not counted, quantitative analysis of the efferent innervation to inner hair cells could not be made. However, a significant loss of myelinated fibres in the osseous spiral lamina after vestibular nerve section confirms that many myelinated efferent fibres are present in this region.

The process of Giant Axonal Neuropathy (GAN) is not restricted to the peripheral nerves, but also involves the central nervous system. In a 25 year old man with normal hair, abundant axon swellings and spheroids were observed in the spinal cord, brain system, and cerebral cortex. The findings in the sural nerve have already been published by Boltshauser et al. (1977). Accumulations of filaments in the axons and in the perineural cells were accompanied by Rosenthal fibres. The ultrastructural pattern of GAN differs clearly from that of Neuroaxonal Dystrophies.

Class I retinal ganglion cells have been identified in wholemounts of rat retinae following injections of horseradish peroxidase (HRP) into retino-recipient nuclei. Class I cells are characterized by relatively large somata, 3-7 fairly frequently branching large-gauge primary dendrites and relatively thick axons. Cells with a very similar morphology have been visualized in the ganglion cell layer of retinal wholemounts using a neurofibrillar stain. The size of the somata and dendritic trees of Class I cells is affected by the density of all classes of ganglion cells: both somata and dendritic trees of Class I cells located in the region of peak density are smaller than those located in medium- and low-density ganglion cell regions. The mean numbers of Class I ganglion cells labelled following massive injections of HRP into retino-recipient nuclei were 876 (in albino rats) and 944 (in hooded rats), while the mean number of cells stained with the neurofibrillar method in albino retinae was 791. Thus, with the total number of positively identified retinal ganglion cells being 110,000-115,000 [Potts et al., 1982; Perry et al., 1983], Class I cells in both strains of rat constitute less than 1% of all retinal ganglion cells. Nevertheless the dendritic fields of Class I cells cover the entire retina. Although Class I cells are distributed relatively evenly across the retina, the density is slightly greater in the lower temporal retina where the bulk of the ipsilaterally projecting fibres originates. While Class I cells represent up to 10% of ipsilaterally projecting retinal ganglion cells in both strains of rat, fewer Class I cells project ipsilaterally in albinos than in hooded rats. All contralaterally projecting Class I cells appear to send branching axons to the superior colliculus and dorsal lateral geniculate nucleus. Class I cells represent a larger proportion of the ganglion cells projecting to the dorsal lateral geniculate nucleus (4-5%) than that of ganglion cells projecting to the superior colliculus (about 1%). The morphology, numbers, distribution and the pattern of the central projections of Class I retinal ganglion cells in rats suggest that they are likely to be homologues of the alpha-type ganglion cells distinguished in carnivores.

Examination of brain biopsies from Alzheimer's patients by electron microscopy revealed two types of filaments in and around the argyrophile plaques. The first neurofibrillary tangles were in degenerating neuronal processes, and each twisted tubule was made up of paired helical filaments. The second type stained for amyloid and had the ultrastructural appearance of amyloid. Amyloid fibril material found in these plaques was studied by means of tilt-stage electron microscopy and compared with X-ray images of scale models of bifilar helix. The model fulfilled the structural criteria established by electron microscopy. These observations confirmed that each amyloid profile was composed of a pair of twisted tubules, each of which measured about 60 A in diameter.

Twelve regions of grey matter from the brains of 25 Beagle dogs, varying from one to over 16 years in age, were serially sectioned and sequentially scanned with a semi-automated sampling stage microscope, in a morphometric search for neuritic plaques, neurofibrillary tangles, and evidence of nerve cell loss. Examination of 227,776 light microscopic fields failed to reveal any senile plaques or neurofibrillary tangles. The neuronal densities, which ranged from 473 to 37,014 nucleolated neurons/mm3, showed no significant relationship with ageing. Neuronal lesions of Alzheimer type may be more typical of the human CNS; and physiological evidence for regionally reduced glucose metabolic rate in this animal model may require other structural alterations for its explanation.

The peroneal and ventral caudal nerves of rats exposed to 2,500 ppm CO until loss of nerve conduction occurred were studied by electron microscopy. Loss of normal axonal and Schwann cell structure was seen at the node of Ranvier. This loss was more prominent in large myelinated fibers, but was also seen in small myelinated fibers at seven and ten days postexposure. At this time, ventral caudal nerve conduction velocity decreased following a transient period of recovery lasting 9 to 13 days. Repair of the node began at 14 to 21 days postexposure, when maximal nerve conduction velocity had returned to normal. Complete normalization of node structure was not seen even 60 days after exposure, in many instances.

A 69-year-old male suffering from progressive dementia died 3 years after the beginning of his disease. The neuropathology of this case revealed the coexistence of senile changes, typical for Alzheimer's disease, and the characteristics of Parkinson's disease, namely, numerous senile plaques and neurofibrillary tangles in the cerebrum and neuronal loss with depigmentation in the substantia nigra and locus caeruleus. Lewy-type inclusions were distributed not only in the pigmented brain stem nuclei, but also diffusely in the CNS. The close nosological relationship between paralysis agitans and Alzheimer's disease is discussed.