RESUMEN

Acquired (non-Wilsonian) hepatocerebral degeneration (AHCD) is an irreversible neurological condition characterized by dementia, dysarthria, and motor disturbances. It has been described in patients with severe liver disease of many causes, and notably in patients with surgically or spontaneously created porto-systemic shunts. We report a case of AHCD in a patient with end-stage liver disease due to alcohol abuse and hepatitis C. In addition, this patient showed pathologic evidence of the less commonly reported "shunt myelopathy" in the absence of a surgically created porto-systemic shunt. The myelopathy was associated with a dramatic vacuolation involving especially the deep motor cortex. Electron microscopy suggested that the vacuolation was due mainly to disruption of abnormal astrocytes.

Asunto(s)

Demencia/etiología , Degeneración Hepatolenticular/complicaciones , Trastornos del Movimiento/etiología , Enfermedades de la Médula Espinal/etiología , Anciano , Encéfalo/patología , Degeneración Hepatolenticular/patología , Humanos , Masculino , Enfermedades de la Médula Espinal/patología

RESUMEN

This report provides the first detailed neuropathological study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in humans. All 3 subjects self-administered the drug under the impression it was "synthetic heroin" and subsequently developed severe and unremitting parkinsonism, which was L-dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time-limited insult to the nigrostriatal system can set in motion a self-perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.

Asunto(s)

1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Sustancia Negra/efectos de los fármacos , Adulto , Muerte Celular , Humanos , Masculino , Sustancia Negra/patología

RESUMEN

In four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa-responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.

Asunto(s)

Demencia/genética , Salud de la Familia , Enfermedad de Parkinson/genética , Adulto , Antiparkinsonianos/administración & dosificación , Colina O-Acetiltransferasa/análisis , Demencia/diagnóstico por imagen , Demencia/tratamiento farmacológico , Dopamina/análisis , Femenino , Genes Dominantes , Hipocampo/química , Hipocampo/enzimología , Hipocampo/patología , Ácido Homovanílico/análisis , Humanos , Levodopa/administración & dosificación , Cuerpos de Lewy/patología , Locus Coeruleus/química , Locus Coeruleus/patología , Masculino , Persona de Mediana Edad , Neostriado/química , Neostriado/patología , Degeneración Nerviosa/patología , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Linaje , Sustancia Innominada/química , Sustancia Innominada/patología , Sustancia Negra/química , Sustancia Negra/patología , Lóbulo Temporal/química , Lóbulo Temporal/enzimología , Lóbulo Temporal/patología , Tomografía Computarizada de Emisión

RESUMEN

A missense mutation of the alpha-synuclein gene has been associated with parkinsonism in a large Italian kindred. Recently, alpha-synuclein was also identified in Lewy bodies. Using reverse transcribed-polymerase chain reaction (RT-PCR) technique, we sequenced the entire coding region of the alpha-synuclein gene using brain tissue from 24 pathologically proven Parkinson's disease cases. No mutations were found in any of the patients, suggesting that a mutation at the coding region of the alpha-synuclein gene is unlikely to be responsible for nigrostriatal degeneration in typical sporadic Parkinson's disease.

Asunto(s)

Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Mutación Puntual , Adulto , Anciano , Análisis Mutacional de ADN , ADN Complementario , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Sinucleínas , alfa-Sinucleína

RESUMEN

BACKGROUND: There is currently controversy as to the frequency of Alzheimer's disease (AD) in elderly persons with schizophrenia. Several studies have reported an increased frequency of AD in elderly schizophrenics, whereas others have found no increase. This issue is important because it has been hypothesized that medications used to treat schizophrenia may exacerbate AD histopathology. METHODS: We examined autopsy cases from a state psychiatric hospital and a Veterans Affairs medical center. Charts were reviewed on 166 subjects to determine if the history warranted a DSM-IV diagnosis of schizophrenia. All subjects had complete gross and microscopic neuropathologic evaluations, which were reviewed for evidence of Alzheimer's disease. RESULTS: Retrospective chart review identified 51 subjects over the age of 55 who met DSM-IV criteria for schizophrenia (mean age = 71.7 years, SD = 8.6, range 56-95 years). Of these 51, only I met neuropathologic criteria for AD, a frequency of 2%. CONCLUSIONS: The frequency of subjects meeting neuropathologic criteria for Alzheimer's disease in our sample of schizophrenics was equal to or less than that found in the general population. Because institutionalized populations may contain an excess of elderly schizophrenic patients with severe behavioral pathologies, which may in turn reflect the presence of neurodegenerative processes such as Alzheimer's disease, our results may actually overestimate the frequency of Alzheimer's in the entire schizophrenic population. The frequency of Alzheimer's disease in the elderly with schizophrenia may be less than that in the general population.

Asunto(s)

Anciano/psicología , Enfermedad de Alzheimer/epidemiología , Esquizofrenia/epidemiología , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Esquizofrenia/patología

RESUMEN

A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa band representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex from 14 cases of typical Parkinson's disease. With a 24-h exposure time, this band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly, the 36-kDa band (as well as other high-molecular-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's disease and Alzheimer's disease. A preliminary analysis of samples from the frontal cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only one instance. The identification of novel alpha-synuclein-immunoreactive bands in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form of familial parkinsonism.

Asunto(s)

Enfermedad de Alzheimer/genética , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Especificidad de Anticuerpos , Western Blotting , Química Encefálica/genética , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Lóbulo Frontal/química , Lóbulo Frontal/patología , Humanos , Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Mutación , Degeneración Nerviosa/genética , Degeneración Nerviosa/patología , Proteínas del Tejido Nervioso/inmunología , Fosfoproteínas/análisis , Fosfoproteínas/inmunología , Sustancia Negra/química , Sustancia Negra/patología , Sinucleínas , alfa-Sinucleína

RESUMEN

The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

Asunto(s)

Alelos , Enfermedad de Alzheimer/genética , alfa 1-Antiquimotripsina/genética , Adulto , Anciano , Apolipoproteína E4 , Apolipoproteínas E/genética , Femenino , Frecuencia de los Genes , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia

RESUMEN

Mutations in the presenilin (PS)-1 and PS-2 genes have been shown to be linked with the development of Alzheimer's disease (AD). We examined Alzheimer's brain tissue by immunohistochemistry using a set of antibodies raised to sequences shared between PS-1 and PS-2 proteins. These antibodies reacted exclusively with a subset of neurofibrillary tangles and not with neuropil threads or dystrophic neurites. Detection of the presenilin epitope in neurofibrillary tangles was observed in sporadic Alzheimer's disease brain samples and in samples from individuals carrying PS-1 and PS-2 mutations with no qualitative difference. These data indicate that both wild-type and mutant PS proteins are involved in a common pathogenic pathway in AD.

Asunto(s)

Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Anticuerpos/química , Proteínas de la Membrana/inmunología , Ovillos Neurofibrilares/inmunología , Ovillos Neurofibrilares/patología , Biomarcadores , Encéfalo/inmunología , Inmunohistoquímica , Presenilina-1 , Presenilina-2 , Proteínas Recombinantes/inmunología

RESUMEN

The presence of beta-amyloid in brain tissue is characteristic of Alzheimer's disease (AD). A naturally occurring derivative of the beta-amyloid peptide, p3, possesses all of the structural determinants required for fibril assembly and neurotoxicity. p3-specific antibodies were used to examine the distribution of this peptide in brain. p3 reactivity was absent or sparse in aged non-AD brains but was prevalent in selected areas of AD brain in diffuse deposits and in a subset of dystrophic neurites. p3-reactive dystrophic neurites were found both independent in the neuropil and associated with plaques. Little or no reactivity was observed to amyloid cores in classical plaques or to amyloid in the cerebral vasculature. The exclusive appearance of p3 reactivity in AD brain plus the selective localization of p3 reactivity to abnormal structures in the temporal lobe limbic system suggests that p3 may be a contributing factor to AD pathology.

Asunto(s)

Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/análisis , Precursor de Proteína beta-Amiloide/análisis , Química Encefálica , Fragmentos de Péptidos/análisis , Enfermedad de Alzheimer/etiología , Secuencia de Aminoácidos , Amígdala del Cerebelo/química , Animales , Corteza Cerebral/química , Hipocampo/química , Hipocampo/patología , Humanos , Inmunohistoquímica , Modelos Genéticos , Datos de Secuencia Molecular , Conejos , Proteínas tau/análisis

RESUMEN

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is generally considered to be nonfamilial. We report a brother and sister with clinical and pathologic findings characteristic of PSP. Both developed parkinsonism in the eighth decade of life and within 5 years exhibited severe postural instability, bradykinesia, rigidity, dystonia, dysarthria, dysphagia, urinary incontinence, pseudobulbar palsy, and supranuclear oculomotor dysfunction but no tremor. Neither responded to levodopa and/or carbidopa. Their mother and, possibly, maternal grandfather reportedly suffered from a parkinsonian syndrome. Essential tremor occurred in the siblings' father and in two of the brother's three children. Autopsy in the brother at age 81 years and sister at age 79 years revealed changes typical of PSP with atrophy and neurofibrillary tangles in the globus pallidus, subthalamic nucleus, and rostral tegmental brainstem. No Lewy bodies were present. These cases are the first pair of relatives reported with autopsy confirmation of PSP in both and raise the question of genetic predisposition to PSP.

Asunto(s)

Parálisis Supranuclear Progresiva/genética , Parálisis Supranuclear Progresiva/patología , Anciano , Autopsia , Encéfalo/patología , Femenino , Humanos , Masculino , Enfermedad de Parkinson/genética , Linaje , Temblor/genética

Asunto(s)

Hipocampo/patología , Cuerpos de Lewy/ultraestructura , Enfermedad de Parkinson/patología , Humanos , Locus Coeruleus/patología , Microscopía Electrónica , Persona de Mediana Edad

Asunto(s)

Amígdala del Cerebelo/patología , Dopaminérgicos/toxicidad , Hipocampo/patología , Cuerpos de Inclusión/ultraestructura , Cuerpos de Lewy/ultraestructura , Intoxicación por MPTP , Anciano , Enfermedad de Alzheimer/patología , Animales , Femenino , Humanos , Masculino , Microscopía Electrónica , Enfermedad de Parkinson/patología , Saimiri

RESUMEN

Eosinophilic neuronal inclusions resembling cortical Lewy bodies have been observed in the amygdala-parahippocampal region of aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys. Electron microscopy in six monkeys revealed a composition of curving bundles of 16-17 nm filaments, arranged in a ball shape or as a cap adjacent to the nerve cell nucleus. The main difference between the monkey inclusions and human cortical Lewy bodies was the random orientation of the filaments in the human inclusion bodies.

Asunto(s)

1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Amígdala del Cerebelo/ultraestructura , Hipocampo/ultraestructura , Cuerpos de Inclusión/ultraestructura , Envejecimiento , Animales , Dopamina/metabolismo , Microscopía Electrónica , Saimiri

RESUMEN

The present study examined neurochemical, morphological and functional markers of the nigrostriatal dopamine system in young, intermediate-aged and old squirrel monkeys. Striking reductions in motoric activity were observed with advancing age. significant age-related loss of dopamine occurred in the substantia nigra (70%) and the putamen (30%) but not in the caudate. There was a strong correlation between the reductions in motoric activity and the loss of putamen dopamine. However, nigrostriatal dopamine loss did not appear to be the consequence of age-related loss of dopaminergic nigral neurons since the number of tyrosine immunoreactive cells was not significantly different among the three age groups. These results suggest that the aging squirrel monkey demonstrates the age-related loss of nigrostriatal dopamine thought to occur in humans and identify this non-human primate as a useful model to further investigate the underlying mechanism(s) and functional consequences of age-related decline of the nigrostriatal dopamine system. In addition, the selective loss of dopamine in the putamen but not the caudate parallels the regional vulnerability observed in Parkinson's disease, an age-related neurodegenerative disorder, raising the possibility of a relationship between normal aging and the development of this disease. Finally, because the number of tyrosine hydroxylase (TH) positive cells remains constant with age, these results raise the possibility that therapeutic strategies aimed at increasing dopamine concentrations may benefit elderly individuals.

Asunto(s)

Envejecimiento/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Sustancia Negra/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Análisis de Varianza , Animales , Recuento de Células , Femenino , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Actividad Motora/fisiología , Saimiri , Serotonina/metabolismo

RESUMEN

We have examined the ultrastructure of the striatum in squirrel monkeys 1-5 d after a single sc injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 2.5 mg/kg. One untreated monkey served as control. We expected to find a dense degeneration of the dopamine terminals, but found instead that the main abnormality consisted of a focal vacuolation of the tissue, perhaps related to the striosome/matrix mosaic of the neostriatum. The vacuolation involved not only terminals, but also other parts of the neuropil. The severity of the destructive process increased from d 1-5. We conclude that MPP+, the toxic metabolite of MPTP, may gain access to the neuropil, either before or after its active uptake into and subsequent destruction of the dopamine terminals. In the present study, abnormalities were observed simultaneously in the striatum and substantia nigra as early as 24 h after MPTP administration. It is, however, possible that the time-course might differ between the two locations with even shorter time intervals or changes in dosage of MPTP.

Asunto(s)

1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Cuerpo Estriado/efectos de los fármacos , Degeneración Nerviosa/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Cuerpo Estriado/fisiopatología , Cuerpo Estriado/ultraestructura , Microscopía Electrónica , Neuronas/ultraestructura , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Saimiri

RESUMEN

The beta-amyloid peptide (beta AP) has been characterized by protein sequencing techniques as a 39-43 amino acid protein with heterogeneous COOH-termini. Controversy exists regarding the predominant form of beta AP in neuritic plaques (NP) and cerebral vasculature of Alzheimer's disease (AD) brain. A monoclonal antibody was developed that selectively recognizes the free COOH-terminal of beta AP 1-42 but not beta AP species with shorter or longer COOH-termini. Brain sections from AD and related disorders were examined using this antibody. In AD samples, the antibody stained diffuse amyloid and NP cores, many intraneuronal and extraneuronal neurofibrillary tangles (NFT), but not cerebrovascular amyloid. Pick and Lewy bodies lacked immunoreactivity. These findings suggest that beta AP 1-42 is present in early and mature amyloid deposits and NFT, but that species of beta AP other than 1-42 comprise human vascular deposits.

Asunto(s)

Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/análisis , Anticuerpos Monoclonales , Química Encefálica , Adulto , Anciano , Animales , Especificidad de Anticuerpos , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Saimiri

RESUMEN

The MPTP monkey model for PD has continued to display similarities as well as differences from the human disease, also in respect to its neuropathology. In 65 MPTP-treated squirrel monkeys with survival for more than 2 days, the main similarities consisted of nerve cell degeneration, not only of SN, but also, in the majority of cases, of the LC. In 13 animals that survived for from 1 to 7 years after their first exposure to MPTP, the nerve cells in the ventrolateral portion of the SN compacta were particularly vulnerable, just as in PD. The principal differences were the lack of progression of the disease process in these long-term animals (although this has yet to be systematically tested) and the absence of formation of typical Lewy bodies in the SN, LC, and other predilection sites for Lewy bodies. Since inclusion bodies, now observed in 16 monkeys, could be produced fairly consistently in aged MPTP-treated squirrel monkeys, they appeared to represent a bridge between these similarities and differences. They had some features, especially their location in predilection sites for Lewy bodies, such as the SN, in common with Lewy bodies, but did not display the fully convincing morphological and immunocytochemical features, characteristics of the human inclusion bodies in PD. Overall, these studies continue to provide tantalizing hints that this model could lead to important new insights into the pathologic process that underlies PD.

Asunto(s)

Intoxicación por MPTP , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson/patología , Animales , Relación Dosis-Respuesta a Droga , Haplorrinos , Humanos , Cuerpos de Inclusión/efectos de los fármacos , Cuerpos de Inclusión/ultraestructura , Cuerpos de Lewy/efectos de los fármacos , Cuerpos de Lewy/ultraestructura , Locus Coeruleus/efectos de los fármacos , Locus Coeruleus/patología , Degeneración Nerviosa/efectos de los fármacos , Degeneración Nerviosa/fisiología , Enfermedad de Parkinson Secundaria/patología

RESUMEN

The nucleus basalis of Meynert (nbM) was examined using immunocytochemistry for beta-amyloid precursor protein (beta APP) expression in Alzheimer's disease (AD). In mild AD cases, light labeling of the cell body and proximal processes was observed, and small intracellular structures were labeled rarely. In the more severe cases, intense cytoplasmic beta APP labeling was seen, often along with small beta APP-positive structures. Double-labeling experiments demonstrated that in the more severe cases these small structures were also decorated by a neurofibrillary tangle (NFT) antiserum. Other neurons in the severe cases showed incorporation of beta APP into large inclusions, which were also labeled with the NFT antiserum. However, some large inclusions in the severe cases were labeled by the NFT antiserum but contained no beta APP. Extraneuronal NFTs did not show beta APP labeling and did not react with an antibody to the beta-amyloid peptide. These results suggest that increased expression of beta APP coincides with intracellular NFT formation in the nbM, but that the formation of extraneuronal NFTs results in a loss of beta APP immunoreactivity.

Asunto(s)

Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Sustancia Innominada/metabolismo , Adulto , Enfermedad de Alzheimer/patología , Síndrome de Down/metabolismo , Síndrome de Down/patología , Humanos , Inmunohistoquímica , Sustancia Innominada/patología

RESUMEN

Previous studies from this laboratory have shown that CNS myelin is phagocytized and metabolized by cultured rat macrophages to a much larger extent when myelin is pretreated with serum containing antibodies to myelin constituents than when it is left untreated or pretreated with non-specific serum. In this study the effect of cerebrospinal fluid (CSF) from rabbits with experimental allergic encephalomyelitis (EAE) in promoting myelin phagocytosis was examined. Fourteen rabbits were immunized with purified myelin in Freund's complete adjuvant, seven of which developed clinical EAE symptoms. Serum and CSF were collected from EAE and control rabbits, and the CSF was centrifuged to remove cells. Sera and CSF from these rabbits and from Freund's adjuvant-immunized controls and untreated controls were measured for IgG content by radial diffusion assay, their myelin antibody characteristics were analyzed by immunoblots, and the ability of these serum and CSF samples to promote myelin phagocytosis when used for myelin opsonization was examined. The ability of a CSF sample to enhance radioactive myelin uptake and phagocytosis by cultured macrophages as measured by the appearance of radioactive cholesterol ester was linearly proportional to its total IgG titer, and correlated approximately both with clinical symptoms of the animal and the presence of antibody against the myelin constituents myelin basic protein, proteolipid protein, and galactocerebroside. The cholesterol esterification activities of EAE sera correlated to a lesser extent with IgG levels and clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Sistema Nervioso Central/metabolismo , Encefalomielitis Autoinmune Experimental/líquido cefalorraquídeo , Macrófagos/metabolismo , Vaina de Mielina/metabolismo , Fagocitosis/efectos de los fármacos , Animales , Ésteres del Colesterol/inmunología , Ésteres del Colesterol/metabolismo , Femenino , Liofilización , Immunoblotting , Inmunodifusión , Inmunoglobulina G/inmunología , Lípidos/aislamiento & purificación , Macrófagos/efectos de los fármacos , Conejos

RESUMEN

Some of the similarities and differences between the neuropathology of Parkinson's disease, Huntington's disease, and Alzheimer's disease have been reviewed, and the relationship between the three diseases has been discussed. Although interconnected and reciprocally innervated structures are affected in PD and HD, they appear less closely related than in PD and AD. Different neurotoxins may play a part in their pathogenesis, as also suggested from other evidence. Neuropathologic features of PD, HD and AD are entirely compatible with a role for neurotoxins in their pathogenesis, but do not by themselves make a strong case for a neurotoxic hypothesis. However, additional neuropathologic studies of experimental neurotoxins may further strengthen arguments in favor of a neurotoxic etiology, as the MPTP animal model is doing for Parkinson's disease. Such experimental studies along with further molecular biological and other sophisticated new methods may open the way for exciting new developments in the near future.

Asunto(s)

Enfermedad de Alzheimer/patología , Encéfalo/patología , Enfermedad de Huntington/patología , Enfermedad de Parkinson/patología , Humanos