Borreliosis and Alzheimer's disease.
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Alzheimer Disease↗
Biomedical subjects
D W Dickson
Publications and source records attributed to D W Dickson.
Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles.
Eleven anti-neurofilament (anti-NF) monoclonal antibodies were studied for their reactivity with heat-stable, microtubule-associated proteins and Alzheimer neurofibrillary tangles (ANT). On immunoblots of NF proteins, the antibodies recognized epitopes that were variably sensitive to Escherichia coli alkaline phosphatase. Eight of the antibodies showed reactivity with ANT and decreased binding to electroblotted NF after phosphatase treatment. The same eight antibodies reacted with tau proteins from bovine and rat brain, binding to tau proteins was also substantially reduced by phosphatase. Of the eight antibodies that bound to animal tau proteins, five also bound to tau proteins from normal human brain. All of the antibodies that bound to animal tau proteins stained ANT in frozen tissue sections. Brief treatment of tissue sections with trypsin in most cases enhanced antibody binding to ANT. All antibodies that lacked reactivity with tau proteins failed to bind ANT. Phosphatase treatment of Alzheimer tissue sections did not change the immunoreactivity of ANT and neurites in senile plaques with ANT-reactive, anti-NF antibodies, except for two antibodies that showed decreased binding to ANT. In contrast, axonal staining was decreased or eliminated by phosphatase treatment, similar to the response of electroblotted NF and tau proteins. These results suggest that staining of ANT by anti-NF antibodies may be due to cross-reaction of anti-NF with epitopes in tau proteins, the epitopes in axons, NF, and tau are sensitive to the effect of phosphatase, whereas the majority of those in ANT are not, and some of the epitopes in ANT that are shared with NF and tau proteins are not readily accessible to antibody binding.
Alzheimer Disease↗
Reduced somatostatin-like immunoreactivity in cerebral cortex in nonfamilial dysphasic dementia.
A nonfamilial syndrome is described in two middle-aged men who presented with progressive aphasia without incipient signs of cognitive impairment. In each case, 2 years elapsed before progressive functional decline or behavioral disabilities supervened. Radiologic studies documented asymmetric left cerebral atrophy that was progressive. The structure of the language disintegration was distinctive and not like that in Alzheimer's disease. Pathologic studies performed at postmortem examination of one patient documented asymmetric cerebral atrophy with nonspecific histopathologic changes. Biochemical studies revealed normal tissue levels of choline acetyltransferase activity, but reduced somatostatin-like immunoreactivity. Since cerebral somatostatin is largely present in intrinsic cortical neurons, while cholinergic innervation is largely derived from the basal forebrain, these findings suggest that nonfamilial dysphasic dementia may be an example of a distinct class of dementia due to intrinsic cortical degeneration, with sparing of the basal forebrain.
Aphasia↗
Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2.
Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2% SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3% polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any given tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.
Alzheimer Disease↗
A neuronal antigen in the brains of Alzheimer patients.
A monoclonal antibody was prepared against pooled homogenates of brain tissue from patients with Alzheimer's disease. This antibody recognizes an antigen present in much higher concentration in certain brain regions of Alzheimer patients than in normal brain. The antigen appears to be a protein present in neurons involved in the formation of neuritic plaques and neurofibrillary tangles, and in some morphologically normal neurons in sections from Alzheimer brains. Partial purification and Western blot analysis revealed the antigen from Alzheimer brain to be a single protein with a molecular weight of 68,000. Application of the same purification procedure to normal brain tissue results in the detection of small amounts of a protein of lower molecular weight.
Alzheimer Disease↗
Pick body-like inclusions in the dentate fascia of the hippocampus in Alzheimer's disease.
Pick body-like inclusions are described in the granular neurons of the dentate fascia in Alzheimer's disease. The inclusions are round, argyrophilic and stained by thioflavine-S. Immunocytochemically they contain antigenic determinants of neurofilaments and of Alzheimer neurofibrillary tangles. Ultrastructurally they are composed primarily of 15-18 nm straight filaments similar to the neurofibrillary pathology of progressive supranuclear palsy and Pick's disease. The dentate fascia inclusions, as well as cerebellar plaques but not amyloid angiopathy, are found most frequently in association with severe neurofibrillary degeneration.
Aged↗
Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes.
Ballooned neurons are histological features of several neurodegenerative diseases of the central nervous system. We describe the immunocytochemical staining of ballooned neurons in Pick's disease, unclassified dementia, corticonigral degeneration, pigment-spheroid degeneration and Alzheimer's disease. In all of these conditions the ballooned neurons contain phosphorylated epitopes recognized by monoclonal antibodies to neurofilaments, but not epitopes unique to Alzheimer neurofibrillary tangles and Pick bodies. The morphological features and immunohistochemical properties of ballooned neurons in these disorders bear resemblance to swollen neurons produced by neurotoxins that impair axoplasmic transport of neurofilaments. This finding, by analogy, suggests that impaired axoplasmic transport of neurofilaments may be a common mechanism in various dementing neurodegenerative diseases.
Aged↗
Cerebral granular cell tumor: immunohistochemical and electron microscopic study.
A rare intracerebral granular cell tumor (GCT) was studied by immunocytochemical and ultrastructural methods. The tumor was composed of two cell types--filament-rich and granular cells. Granular cells contained PAS-positive, diastase-resistant granules that ultrastructurally corresponded to autophagic cytosegresomes. Glial fibrillary acidic protein, the intermediate filament protein specific for astrocytes, was demonstrated in the filament-rich and, to a lesser extent, in the granular cells. Unlike noncerebral GCT, neither S-100 protein nor vimentin was detected in the tumor cells. On the other hand, both cerebral and noncerebral GCT were labeled immunocytochemically with peanut lectin (Arachis hypogaea). The results suggest that cerebral GCT share some features with noncerebral GCT, but differ in other respects. They further suggest that GCT may be derived from different cell types depending on the tissue of origin, and that cerebral GCT may be derived from astrocytes.
Adult↗
Klüver-Bucy syndrome and amyotrophic lateral sclerosis: a case report with biochemistry, morphometrics, and Golgi study.
We studied a patient with amyotrophic lateral sclerosis and the Klüver-Bucy syndrome. At autopsy there was extensive degeneration of the limbic system with the brunt of the changes in the medial temporal lobe, especially the entorhinal cortex and subiculum. Degenerative changes were also seen in the substantia nigra and lower motor neurons. Morphometric and biochemical studies implied a disease process that affected small, possibly somatostatinergic, cortical neurons. These latter findings and the lobar distribution of cortical atrophy were consistent with Pick's disease, but Pick bodies and ballooned neurons were not present.
Affective Symptoms↗
AIDS: calcification of the basal ganglia in infants and children.
CT or postmortem examination demonstrated calcification of the basal ganglia in eight infants and children with acquired immune deficiency syndrome. Serial CT studies documented progression of both bilateral symmetric calcium densities and cerebral atrophy. Clinical features included progressive encephalopathy with dementia, and pyramidal tract signs. Postmortem examination of four children revealed variable degrees of calcific vasopathy of the basal ganglia, involving predominantly the putamen and globus pallidus.
Acquired Immunodeficiency Syndrome↗
Multinucleated giant cells in acquired immunodeficiency syndrome encephalopathy. Origin from endogenous microglia?
Multinucleated giant cells that are characteristic of the encephalomyelopathy of acquired immunodeficiency syndrome are stained by a lectin histochemical method. The particular lectin used, Ricinus communis agglutinin I, has been shown to bind to endogenous microglial cells in human brain, as well as to endothelial cells of blood vessels. These results suggest that multinucleated giant cells in the brain of patients with acquired immunodeficiency syndrome may be derived from endogenous microglia.
Acquired Immunodeficiency Syndrome↗
Immunoreactive keratin with foreign body reaction in anencephaly.
Keratinous material, in the form of epithelial squames often with foreign body reaction and dense gliosis, was demonstrated in all of ten cases of anencephaly by a sensitive and specific immunohistochemical stain. In some cases keratin was not recognized on routine histological stains.
Anencephaly↗
Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides.
Ten monoclonal antibodies to Alzheimer neurofibrillary tangles (ANTs) were produced by immunizing mice with a brain homogenate from senile dementia of the Alzheimer type (SDAT). In methanol-fixed isolated neuronal perikarya, six of these antibodies reacted with nearly every ANT, three recognized 70-88% of ANTs, and one bound to less than 30% of ANT. In paraffin sections, three of the antibodies did not bind to tangles that had been fixed in formalin, three stained weekly, and four reacted with tangles in tissues that had been in formalin for more than a decade. Immunoblotting of brain homogenates showed that all but one antibody reacted with proteins from SDAT samples insoluble in SDS and too large to enter even the 3% polyacrylamide stacking gel. Polypeptides extractable by Tris buffer of molecular weight 58, 66, and 70 kd were detected in both normal and SDAT brains by two antibodies and only in SDAT brain by two other antibodies. One antibody did not show any reaction on the immunoblot. The results demonstrate that the epitopes recognized by these antibodies are not identical and that ANTs contain unique antigenic determinants as well as determinants in common with normal brain. Whether the unique determinants are acquired during tangle development or are essential in tangle formation remains to be investigated.
Alzheimer Disease↗
Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy.
Neurofibrillary degeneration is an argyrophilic intraneuronal lesion found in several unrelated neurologic conditions. The relationship between different types of neurofibrillary tangles is investigated with two monoclonal antibodies raised against Alzheimer neurofibrillary tangles (anti-ANT). Using the peroxidase-antiperoxidase technique, the authors demonstrate that neurofibrillary tangles of progressive supranuclear palsy, containing 15-nm straight filaments, share an antigenic determinant with ANTs. Ultrastructural studies localize the antigenic determinant to filamentous elements in the parakarya. The determinant is not present in normal brain, aluminum-induced experimental tangles in the rabbit, Lewy bodies, Hirano bodies, or axonal filamentous inclusions of amyotrophic lateral sclerosis and giant axonal neuropathy. It is, however, present in ANTs regardless of the pathologic condition in which they are found, including Alzheimer's disease, Down's syndrome, and postencephalitic Parkinson's disease.
Alzheimer Disease↗
Medulloblastoma with glial and rhabdomyoblastic differentiation. A myoglobin and glial fibrillary acidic protein immunohistochemical and ultrastructural study.
This is a report of an unusual, densely cellular, midcerebellar neoplasm in a seven-year-old boy. Although clinically consistent with a medulloblastoma, immunohistochemistry and electron microscopy demonstrated glial and rhabdomyoblastic differentiation in the tumor. We discuss the differential diagnosis of this tumor as it relates to glial differentiation in medulloblastomas and the myogenic potential of primitive neuroectoderm.
Cerebellar Neoplasms↗
Regional distribution of tyrosine hydroxylase and dopamine beta-hydroxylase activities in guinea pig heart.
The sympathetic and parasympathetic autonomic nervous systems regulate heart rate and myocardial contractility. Using sensitive radioisotopic assays, we examined the regional distribution of tyrosine hydroxylase and dopamine beta-hydroxylase activity, which are markers for sympathetic autonomic innervation, in specialized pacemaker and conduction tissue and in contractile heart tissue. Of the 20 regions of guinea pig heart examined, we find that the highest activities occur in the sinoatrial node and the right atrial appendage. Intermediate activity occurs in the left atrium, interatrial septum and right ventricular papillary muscle. Activities in the remainder of the heart are lower and rather uniform. Comparing the enzyme markers for the parasympathetic [17] and sympathetic system, we find that these systems have different distributions. The former, for example, is closely associated with the specialized pacemaker and conduction system including the sinoatrial and atrioventricular nodes and regions rich in Purkinje fibers. The sympathetic system, on the other hand, is associated with both contractile and conducting tissue.
Adrenergic Fibers↗
Beta-amyloid deposition and paired helical filament formation: which histopathological feature is more significant in Alzheimer's disease?
Clinicopathological, biochemical, immunochemical and molecular biological studies of beta amyloid and neurofibrillary changes have been recently described by this and other laboratories. Although amyloid deposition is present in every AD brain, it is also present, sometimes in great quantities, in nondemented individuals. On the other hand, paired helical filament formation in perikarya (neurofibrillary tangles) and the neuropil of the cerebrum appears to be the histopathological feature that is most characteristic of AD.
Alzheimer Disease↗
Identification of normal and pathological aging in prospectively studied nondemented elderly humans.
Results of a standardized histochemical and immunocytochemical analysis of the brains of 14 nondemented elderly humans for whom prospective neurological and neuropsychological data had been collected for 3 to 8 years before death suggested that nondemented elderly humans fall into two pathological subgroups that are not clinically distinguishable. One was associated with moderate to marked cerebral amyloid deposition ("pathological aging"), while the other had either minimal or no amyloid deposition ("normal aging"). Neocortical and hippocampal neurofibrillary degeneration was either completely absent or of very limited degree in both subgroups. Both subgroups had ubiquitin-immunoreactive dystrophic neurites in the cerebral cortex and granular degeneration of myelin in white matter. These ubiquitin-immunoreactive structures seem to be a universal and invariant manifestation of brain aging, but the same cannot be said for amyloid deposition and neurofibrillary degeneration. Pathological aging might be preclinical Alzheimer's disease, but it currently cannot be distinguished from normal aging by even sensitive neuropsychological measures. These findings provide strong support for the hypothesis that cerebral amyloid deposition is not necessarily associated with clinically apparent cognitive dysfunction and that additional factors, such as neuronal or synaptic loss or widespread cytoskeletal aberrations, are necessary for dementia in AD.
Aged↗