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07-26-2007, 09:53 AM | #11 | ||
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Abstract
Case Report A sporadic case of Creutzfeldt–Jakob disease with beta-amyloid deposits and alpha-synuclein inclusions Anne Vital,11Neuropathology Department, Victor Segalen – Bordeaux 2 University, Bordeaux,Anne Vital, MD, PhD, Laboratoire de Neuropathologie BP 42, Université Victor Segalen, Bordeaux 2, 146, rue Léo-Saignat, 33076 Bordeaux Cedex, France. Email: anne.vital@chu-bordeaux.fr Marie-Hélène Canron,11Neuropathology Department, Victor Segalen – Bordeaux 2 University, Bordeaux, Roger Gil,22Neurology Department, Poitiers University, Poitiers and Jean-Jacques Hauw33Neuropathology Department, Pitié-Salpêtrière Hospital, Paris, France and Claude Vital11Neuropathology Department, Victor Segalen – Bordeaux 2 University, Bordeaux, 1Neuropathology Department, Victor Segalen – Bordeaux 2 University, Bordeaux, 2Neurology Department, Poitiers University, Poitiers and 3Neuropathology Department, Pitié-Salpêtrière Hospital, Paris, France Anne Vital, MD, PhD, Laboratoire de Neuropathologie BP 42, Université Victor Segalen, Bordeaux 2, 146, rue Léo-Saignat, 33076 Bordeaux Cedex, France. Email: anne.vital@chu-bordeaux.fr Abstract Neurodegenerative disorders are characterized by the correlation of clinical symptoms and neuropathological changes in the brain. However, overlaps between distinct entities are becoming more and more evident. We report the coexistence of Alzheimer pathology and alpha-synuclein inclusions in a sporadic, methionine/valine type 1, Creutzfeldt–Jakob disease (CJD) case. There were neurofibrillary changes in the neocortex and beta amyloid cerebral angiopathy was marked. Several Lewy bodies were present in the substantia nigra, locus ceruleus and the dorsal motor nucleus of the vagus, and alpha-synuclein cytoplasmic inclusions were also found in cortical neurons. These findings raise the debated relationship between Parkinson’s disease with dementia, dementia with Lewy bodies and a Lewy body variant of Alzheimer disease. Among the factors that may have contributed to this considerable morphological overlap are the patient’s age (79 years at autopsy) and the over 2-year duration of the disease. As the average disease duration in sporadic methionine/valine type 1 CJD is less than 6 months, it seems legitimate to speculate that the initial symptoms resulted from Alzheimer and alpha-synuclein related pathologies. This observation shows that CJD can be present in elderly patients who are suspected of having other neurodegenerative diseases, which could underline the importance of neuropathology-based surveillance systems. http://www.blackwell-synergy.com/doi...9.2007.00755.x TSS |
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08-16-2007, 01:21 PM | #12 | ||
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Clinico-Pathological Correlation in Dementias
F. TeixeiraI, E. Alonso2, V. Romerol, A. Ortiz', C. Martinez3, E. Otero4 'Departnents of Experimental Neuropathology and 2Genetics, and the 3Division of Psychology and 4Neurology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Submitted: February 22, 1994 Accepted: February 9, 1995 The object of this study is to investigate whether or not there are clinical signs and symptoms in patients with dementia that, by themselves or jointly, can be associated with the pathological diagnosis of Alzheimer's disease. Twelve patients with dementia were studied, in whom the clinical diagnosis of Alzheimer's disease was made according to established criteria. A sample of leptomeninges, cortex and subcortical white matter was obtained from each patient and was processed for light and electron microscopy. In the cases in whom neuritic plaques and neurofibrilary tangles were present, pathological changes were quantified. The diagnosis of Alzheimer's disease was confirmed in 5 cases, whereas in 3 patients spongiform encephalopathy was present. In the remaining patients, the number of neuritic plaques was within normal limits for the age of the subjects. Comparison of the data in Alzheimer (n = 5) and non-Alzheimer (n = 7) groups showed an increased, statistically significant incidence of acalculia, abnormalities of judgment, impairment of abstraction and primitive reflexes in the former. Although good fitting models were obtained, none achieved perfect discrimination. The model that included alterations ofjudgment and acalculia gave the best fit. Key Words: Alzheimer's disease, dementia INTRODUCTION Several signs and symptoms have been described extensively in the various diseases that lead to dementia. These symptoms include lack of attention, defective memory, apathy, emotional lability, judgment changes and delirium (Karp and Mirra 1986). Many of these characteristics, as well as electrophysiological changes, are said to be shared by different forms of dementia (McKhann et al 1984). It is the object of this paper to investigate whether or not, in Alzheimer's disease, there is a constellation ofclinical data that will allow the clinician to reach the diagnosis without the aid of a brain biopsy. Address reprint requests to: Dr F Teixeira, Instituto Nacional de Neurologfa y Neurocirugia, Insurgentes Sur, 3877, Mexico 14269, DF, Mexico. METHODS Twelve patients were studied. Because of degeneration of the patient's brain functions, a detailed medical history was obtained from family members. A complete clinical examination was performed, including cranial nerves, tone, reflexes, coordination, gait and proprioception. None ofthese patients had a history or clinical findings suggestive of other causes of dementia such as cerebral infarction, trauma to the head, intracranial neoplasia, substance abuse or systemic or neurological diseases associated with dementia. Neuropsychological examination was designed by the Division of Psychology of the National Institute of Neurology and Neurosurgery so that the exploration could be adapted to the sociocultural level and schooling of the patients. Basic neuropsychological exploration investigated JPsychiatry Neurosci, VoL 20, No. 4, 1995 276 Dementia Table 1 Degree of psychological deterioration expressed as percentages Degree of deficit Marked (%) Moderate/slight (%) 77 82 84 100 60 66 100 23 18 16 0 20 28 0 Nil (%) 0% 0% 0% 0 20 6 0 Gnosias 66 22 12 R & D): repetition and denomination; I & I: ideomotor and ideatory; VI, P & C: visuomotor integration, perception and coordination. attention, concentration, memory (immediate, recent, remote and learning), language (flow, repetition denomination and comprehension), praxis (ideomotor, ideatory and visuoconstructive) and all modalities of gnosias. Degrees of impairment in each patient were qualified as follows, per different area: 0 = nil, 1 = slight to moderate, and 2 = severe. In 7 patients, a scale was used to assess 5 different aspects of the ability to perform everyday activities: personal hygiene, work, interpersonal relation, motor system (abnormal movements, gait) and memory and visuospacial Qrganization. The scale consists of 100 tests, each one graded as follows: 0 = normal; I = slight deficit; 2 = moderate deficit, and 3= severe deficit. Normal subjects score 20 points or less. The patients underwent an extensive battery of laboratory and neuroimaging studies to evaluate the degree and topography of cerebral atrophy, to exclude vascular impairment and causes of partially or completely reversible dementias. This detailed work-up included a complete blood count, erythrocyte sedimentation rate, Chem 20, thyroid tests, levels of B12, syphilis serology, HIV testing, chest X-ray, electrocardiogram, examination of cerebrospinal fluid, computerized tomographic scanning, and magnetic resonance imaging. Baseline electroencephalographic measures were used to follow the course of the disease. The latency and amplitude of P 300 cognitive-evoked potential were correlated with neuropsychological deterioration. After the studies were completed, the relatives were briefed on the risks of a brain biopsy and on its nature, i.e., that the biopsies are not curative, but part of research protocol to study changes in blood-brain barrier in Alzheimer's disease that is still in process. This protocol was approved by the Committee for Ethics in Biomedical Research from the National Institute of Neurology and Neurosurgery. After permission for the biopsy was granted in writing, a sample of the superior frontal gyrus was taken, as this adds the least operative time and risk. In addition, quantitative studies by de la Monte (1989) showed that, in Alzheimer brains, the regional distribution ofplaques and tangles usually correlates with the distribution of cerebral atrophy. In all of this study's patients, neuroimaging studies revealed that the frontal gyri were severely affected. The s4mple, which included the leptomeninges, cerebral cortex and subcortical white matter, was divided into 2 parts. The first part of the specimen was fixed in buffered formalin and embedded in paraffin. Sections were stained with hematoxylin and eosin; luxol fast blue-cresyl violet was used for myelin and nerve cells; Bielschowsky and Von Braunmuhl methods were used for neurofibrillary tangles and neuritic plaques; and Congo Red was used for amyloid. Immunoperoxidase techniques, using monoclonal mouse antibodies to human beta amyloid and to amyloyd A4 component (Dako A/S, Denmark), were also applied. Senile plaques and neurofibrillary tangles were counted at 100 x power and 400 x power, respectively, on the whole surface of the cortex contained in sections stained with silver methods or immunoperoxidase techniques. Their numbers were expressed per square millimeter unit. The second part of the specimen was finely sectioned and fixed in 2.5% glutaraldehyde in 0.1 M cacodylate buffer, pH 7.4, post-fixed in 1% osmium tetroxide in the same buffer, dehydrated in acetone and embedded in Epon. Semithin sections were stained with toluidine blue and examined under a light microscope. Ultrathin sections, in the silver/grey area of the spectrum of interference colors, were stained with uranyl acetate and lead citrate and observed under a Zeiss EMIO transmission electron microscopy. Attention Concentration Memory Language Fluidity R&D Praxias I&I VI, P & C .-I.. IL I-I 277 July 1995 Journal ofPsychiatry & Neuroscience The following packages were used for statistical analysis of the results: BMDP 1990 version on a VAX 11n750, and GLIM 3.77 version on an AT microcomputer with coprocessor. Pearson's Chi-Square Test and Fisher's Exact Test were used to compare clinical features. RESULTS The results of clinical and laboratory examinations did not rule out Alzheimer's disease in any of the patients, according to established criteria (McKhann et al 1984). There were no instances of hypothyroidism, or cardiac, renal or hepatic malfunction. Cerebrospinal fluid examination was normal in all patients. Computerized tomographic scanning and magnetic resonance imaging showed, in all individuals, global cerebral atrophy with marked reduction in overall crosssectional areas of the brain, an increase of the volume of the ventricular system and of the subarachnoid space. No areas of cerebral infarction were seen in any of the images. Results of the basic neuropsychological exploration are expressed in Table 1. Eighty-eight percent of the patients showed a marked deterioration of judgment and a similar deficit in the performance of abstract tasks and calculation. The mean score of the 7 subjects tested for everyday activity scales was 49, which reflects marked deterioration, and indicates a requirement for permanent assistance and care. In summary, there was a severe degeneration of superior cerebral functions involving cortical and subcortical areas. At this advanced stage of dementia, it is not possible to detect significant differences of involvement among several areas. Five patients (numbers 8 to 12) were diagnosed as having Alzheimer's disease with base on morphologic criteria determined by Khachaturian et al (1985) and Crystal et al (1988). They had numerous neuritic plaques and a variable density of neurofibrillary tangles. Three patients (5 to 7) showed numerous small (1 to 12 micrometer in diameter) vacuoles, many of them confluent, which markedly distorted the neuropil of the cortex. There was severe astrocytic gliosis. No plaques or tangles were seen in these biopsies, and no congophilic or A4 positive material was present. Electron microscopy showed that these vacuoles were located in the cytoplasm of astrocytes and neurons, and contained cytoplasmic and membranous debris. These cases were diagnosed as having Jakob-Creutzfeldt disease. Patients 1 to 3 had few neuritic plaques; their biopsy was reported as being normal for their age. In patient 4, many neurons were atrophic, with dense nuclei and abundant cytoplasmic lipofuscin. These neurons were located far from the surgical margins of the specimen and belonged to all cortical layers. In none of the biopsies were there cytoplasmic or nuclear abnormal bodies, inflammation, neoplasia or demyelination. On the basis of the result of the brain biopsy, the patients were divided into two groups: A (Alzheimer group: patients 8 to 12) and NA (non-Alzheimer group, patients 1 to 7). Individuals from either group were similar in regard to age and sex distribution (see Table 2). In many patients, the number of cortical argyrophilic plaques exceeded by far the minimum established by Khachaturian et al (1985) for each age. Differences between mean numbers ofplaques and neurofibrillary tangles in A and NA subjects were highly significant. Time of evolution tended to be shorter in NA cases, but the difference with the A group was not significant because of the presence of patient 1, who had an unusually long course. Clinico-pathological correlation Family history Two patients had one or more first-degree relatives with dementia. Patient 1 was 83 years old at the time of the biopsy, and his intellectual deterioration had been progressing for 10 years. His sister, aged 71, had a similar clinical picture with 15 years' evolution. This patient had few argyrophilic plaques and no neurofibrillary tangles; this pattern was considered within normal limits for his age. Patient 9, a 52-yearold woman whose diagnosis of Alzheimer's disease was confirmed by brain biopsy, belonged to an extraordinary family in that her mother, her maternal grandmother, a brother, a sister and a maternal aunt had all died after presenting a clinical picture similar to hers. Two other sisters were demented and still alive. The pattern of inheritance for this family corresponds to an autosomal dominant. Pearson's Chi-Square Test showed no statistically significant difference for this variable between the A group and the NA group. Seizures This variable was observed in 3 patients. Patient 8 of the A group, who had a 36-month history of behavioral changes, presented 3 episodes of generalized seizures in the last 4 months before being admitted. Patients 5 and 7, with spongiform encephalopathy, also had convulsive episodes in the last 5 months before being admitted. The difference of incidence between the two groups was not significant. Speech abnormalities Three out of five patients with Alzheimer's disease presented with speech abnormalities, characterized by reduced fluidity and problems for expression and comprehension. Verbal expression was, in the most severely affected patients, reduced to stereotypes, with no residual ability to communicate ideas. Patient 6 of the NA group had marked problems communicating verbally, and was limited to mumbling one of the last words said by the interviewer. The statistical significance for this variable was moderate (p < 0. 1). 278 VoL 20., No. 4,1995 July 1995 Table 2 Clinical and pathological data Case Diagnosis Age Sex Evolution (months) NFI NP 1 Non-Alzheimer 83 M 120 0 8 2 Non-Alzheimer 68 F 66 3 5 3 Non-Alzheimer 43 M 9 0 1 4 Non-Alzheimer 57 F 15 1 0 S Non-Alzheimer 56 M 16 0 0 6 Non-Alzheimer 68 F 5 0 0 7 Non-Alzheimer 61 F II 0 0 Mean 62.29 34.57 0.57 2.0 sd 12.49 M =43% 43.01 1.13 3.21 8 Alzheimer 77 M 60 2 23 9 Alzheimer 52 F 72 8 16 10 Alzheimer 65 F 36 5 14 11 Alzheimer 69 M 19 3 35 12 Alzheimer 59 F 84 6 21 Mean 64.40 54.20 4.8 21.80 sd 9.53 M = 40% 26.50 2.39 8.23 F= 0.10 0.45 17.1 34.36 p n.s. n.s. n.s. p <0.01 p < 0.01 Age is expressed in years; NFT = numbers of neurofibrillary tangles per square millimeter; NP = numbers of neuritic plaques per square millimeter; n.s. = not significant. Cerebellar changes All patients with Alzheimer's disease performed adequately at the tests for coordination, albeit slowly. Among the NA patients, only one woman (number 6) showed generalized incoordination, with dysmetria and truncal ataxia. There was no significant difference between the A group and the NA group regarding this variable. Delirium Relatives of most patients from both groups attested to delirious episodes, with restlessness, visual and auditory hallucination and disorientation. There was no significant difference between the groups. Abnormal movements These movements manifested as intentional tremor of hands. Again, the difference was not significant. None of the cases diagnosed histologically as Jakob-Creutzfeldt disease had myoclonic jerks. Pyramidal abnormalities Three subjects for each group showed mild generalized spasticity, gastrocnemial clonus and bilateral Babinski sign. The difference was not significant. Primitive reflexes Suction, searching, palmar and plantar grasping reflexes were present in all patients with Alzheimer's disease and 3 out of 7 NA individuals. The level of significance was p <0.04. Impairment ofmemory Impairment involves both short-term and long-term memory consolidation and retrieval. All patients with Alzheimer's disease were severely affected, as were 5 out of 7 from the NA group. The remaining 2 NA subjects showed a moderate to slight impairment. There was no statistically significant difference between the A group and the NA group. Impairment ofabstraction, Judgment alterations and acalculia The first 2 features were characteristic of Alzheimer cases and were present in all patients. Acalculia was observed in all patients with Alzheimer's disease but one, in contrast to 1 out of 7 NA cases. In some A individuals, acalculia presented early in the course of the disease. Regarding all 3 features, there was a significant difference (p < 0.05) between the A group and the NA group. Dementia 279 Journal ofPsychiatry & Neuroscience Table 3 Summary of clinical variables in Alzheimer (A) and non-Alzheimer (NA) patients (see text) A Group NA Group n=5 Family history Seizures Speech changes Cerebellar abnormalities Delirium Abnornal movements Pyramidal abnormalities Primitive reflexes Impaired memory Impaired abstraction Judgment alterations Acalculia Dysarthria Apraxia Agnosia T-s 1 2 3 0 4 2 3 5 S S 5 4 2 2 2 Incontinence I Disorientation 3 Abnormal EEG 5 n.s.: difference statistically not significant; +: 0.05 < p < 0.10; ++: p < 0.05. n=7 1 1 5 3 3 3 5 2 1 4 3 4 1 3 Significance n.s. n.s. n.s. n.s. n.s. n.s. n.s. ++ n.s. ++ ++ ++ n.s. n.s. n.s. n.s. n.s. Dysarthria, apraxia and agnosia There was no significant difference in any ofthese features between the A group and the NA group. Incontinence Although this symptom was more common in the NA group, the difference was, once more, not significant. Disorientation Three out of five patients with Alzheimer's disease were disoriented in time and space, compared with 1 out of 7 NA patients. The difference was not significant. Abnormal EEG Electroencephalographic changes, characterized by deficient organization and a generalized slow activity was found in all A patients, and in 3 out of 7 NA patients. The significance of the difference was moderate (p < 0.07). None of the patients presented headache, fever, vertigo or cranial nerve changes. The above discussed variables are shown in Table 3. Logistic discriminant functions The joint effects of the variables were selected in stages because of the small sample size. Although good fitting models were obtained, none achieved a perfect discrimination. Among the models with two variables, alterations in judgment and acalculia gave the best fit (deviance 4.50 with 9 d]) and only I patient with Alzheimer's disease was misclassified (see Table 4). DISCUSSION The rates of accuracy of the clinical diagnosis of Alzheimer's disease in several clinico-pathological studies range from 43% to 87% (Joachim et al 1988; Mosla et al 1985; Muller and Schwartz 1978; Nott and Fleminger 1975; Sulkava et al 1983; Todorov et al 1975; Wade et al 1987). It should be interesting, therefore, if selected clinical data could help to reach this diagnosis without the aid of a brain biopsy. The results of this study show a very significant association of Alzheimer's disease with the following variables: primitive reflexes, impairment of abstraction, changes in judgment and acalculia. In studying the joint effect of 280 VoL 20, No. 4,1995 July 1995 Dementia 281 Table 4 Fitting model including alteradons ofjudgment and acalculia Case Diagnosis Fitted I NA 0.250 2 NA 0.000 3 NA 0.250 4 NA 0.250 5 NA 0.000 6 NA 0.000 7 NA 0.000 8 A 1.000 9 A 1.000 10 A 1.000 11 A 0.250+ 12 A 1.000 NA = non-Alzheimer; A = Alzheimer; + = misclassified Alzheimer patient variables, it was seen that alterations of judgment and acalculia produced the best fit. The sample in this study may be considered small for the purpose of selecting a set of signs and symptoms that can characterize Alzheimer's disease clinically. However, it is not an easy task to obtain the permission to perform a brain biopsy which is of no benefit for the patient when the relative is informed of the risks involved. The definite diagnosis of Alzheimer's disease depends on the microscopical examination of brain tissue, either by autopsy or biopsy. In the USA, the Alzheimer Disease Research Center of the University of Pittsburgh has launched a public campaign to encourage relatives of demented patients to request a postmortem examination of the brain (Boller et al 1989). However, in Mexico, a similar campaign has enjoyed little success so far for several reasons. The patient who suffers from Alzheimer's disease usually dies at home. The relatives, who are already exhausted by the demands of caretaking, obtain a death certificate from the family physician, and proceed quickly to the funeral rites. The few families who do request an autopsy are almost invariably denied admission to the hospital where the patient had been admitted because cadavers without a death certificate must be sent to the police department for autopsy. Many patients die in small towns or villages where there are no pathologists, let alone neuropathologists. Therefore, brain biopsy remains the only possibility for confirming the clinical diagnosis. It is true that there is no benefit derived by the patient from this procedure and that he or she faces surgical and anesthetic risks. In contrast, brain biopsy allows: 1. the development of new diagnostic procedures that might, in the future, replace it; 2. adequate genetic counselling in cases with an autosomal dominant pattern of inheritance, so that family members can take part in studies at the molecular biology level; and 3. the performance of therapeutic trials and of epidemiological surveys in Mexico. Familiar aggregation has been demonstrated in 40% of cases of Alzheimer's disease. In 15% of these cases, the pattern of inheritance was autosomal dominant (Heston et al 1981). Patient number nine's family is an example of the latter, and showed an early age of onset. Vacuolar change, similar to that present in Jakob- Creutzfeldt disease, has been described in brains of patients with Alzheimer's disease, especially at the medial temporal isocortex, where it has a high, statistically significant association with the presence of large numbers of neurofibrillary tangles and argyrophilic plaques (Smith et al 1987). This study considered the possibility that cases 5 to 7, diagnosed as Jakob-Creutzfeldt disease, could be, in fact, Alzheimer cases with this peculiar vacuolar change. A good method for separating the two entities would be the use of antibodies against prion (Pr-P) proteins (Tateishi et al 1988), which were, unfortunately, not available to the authors. However, none of these cases showed positivity for A4 protein, neither had one single argyrophilic plaque or tangle. Moreover, the biopsies were taken from the frontal regions, which are reported to be free of involvement in instances of Alzheimer's disease with vacuolar changes (Smith et al 1987). Although the diagnosis of probable Alzheimer's disease was made in all of the patients in this study, according to the criteria established by McKhann et al (1984), this diagnosis was confirmed in only 47.1% of them. This low rate might be the result of several factors. The National Institute of Neurology and Neurosurgery in Mexico City is an institution that concentrates especially on difficult or unusual cases that are referred from all over the country. Therefore, it received a biased sample that included as many as 3 cases of spongiform encephalopathy. In addition, it is important to remember that a small, 1 cubic centimeter sample of cortex and white matter may not be representative of the extent of the damage in other areas of the brain, and so, correlates poorly with the clinical picture. This illustration is particularly true of cases 1 to 4, which did not fit into any of the pathological entities that manifest clinically as dementia. To understand more clearly the relation between damage and clinical impairment, further prospective studies using autopsy material are needed. REFERENCES American Psychiatric Association. 1987. Diagnostic and statistical manual of mental disorders. 3rd ed., revised. Washington DC: American Psychiatric Association. 282 Journal ofPsychiaty & Neuroscience VoL 20, No. 4,1995 Boller F, Lopez OL, Moossy J. 1989. Diagnosis of dementia: clinicopathologic correlations. Neurology 39:76-79. Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L. 1988. Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38: 1682-1687. De la Monte SM. 1989. Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer's disease. Ann Neurol 25:450-459. Heston LL, Mastri AR, Andersen E, White V. 1981. Dementia of the Alzheimer type. Arch Gen Psychiat 38:1085- 1090. Joachim CL, Morris JH, Selkoe DJ. 1988. Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases. Ann Neurol 24:50-56. Karp HR, Mirra SS. 1986. Dementia in adults. In: Joynt RJ, editor. Clinical neurology. Philadelphia PA: Lippincott. pp 1-74. Khachaturian ZS. 1985. Diagnosis of Alzheimer's disease. Arch Neurol 42:1097-1104. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 1984. Clinical diagnosis of Alzheimer's disease. Neurology 34:939-944. Mosla PK, Paijarvi L, Rinne JO, Rinne UK, Sako E. 1985. Validity of clinical diagnosis in dementia: a prospective clinicopathological study. J Neurol Neurosurg Psychiatry 48:1085-1090. Muller HF, Schwartz G. 1978. Electroencephalograms and autopsy findings in geropsychiatry. J Geront 4:504-513. Nott PN, Fleminger JJ. 1975. Presenile dementia: the difficulties of early diagnosis. Acta Psychiatr Scand 51: 210- 217. Smith TW, Anwer U, DeGirolami U, Drachman DA. 1987. Vacuolar change in Alzheimer's disease. Arch Neurol 44:1225-1228. Sulkava R, Haltia M, Paetau A, Wikstrom JU, Palo J. 1983. Accuracy of clinical diagnosis in primary degenerative dementia: correlation with neuropathological findings. J Neurol Neurosurg Psychiatry 46:9-13. Tateishi J, Tetsuyuki K, Mashigu Chi M, Shii M. 1988. Gerstmann Straussler-Scheinker disease: immunohistological and experimental studies. Ann Neurol 24:35-40. Todorov A, Go R, Constantinidis J, Eiston R. 1975. Specificity of the clinical diagnosis of dementia. J Neurol Sci 26:81-98. Wade JPH, Mirsen TR, Hachinski VC, Fisman M, Lau C, Merskey H. 1987. The clinical diagnosis of Alzheimer's disease. Arch Neurol 44:24-29.tss |
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09-27-2007, 11:42 AM | #13 | ||
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Greetings all,
i thought some of you might find interest in this meeting of the mad cow minds i.e. what i call the 'prion gods'. about 143 pages of the latest 'abstracts' TSE science and there is data on the AA amyloidosis, Alzheimer's.........tss PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007 Date: Mon, 24 Sep 2007 21:31:55 -0500 I suggest that you all read the data out about h-BASE and sporadic CJD, GSS, blood, and some of the other abstracts from the PRION2007. ... http://lists.ifas.ufl.edu/cgi-bin/wa...&F=&S=&P=19744 USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS http://lists.ifas.ufl.edu/cgi-bin/wa...mg&T=0&P=19779 see full text 143 pages ; http://www.prion2007.com/pdf/Prion%2...0Abstracts.pdf Terry S. Singeltary Sr. Bacliff, Texas |
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10-08-2007, 04:42 PM | #14 | ||
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P01.34
Pathological Interaction Between Protein Misfolding Disorders: Prions and Alzheimer's Disease Morales, R; Estrada, L; Castilla, J; Soto, C University of Texas Medical Branch, Neurology, USA Protein Misfolding Disorders (PMD) include several diverse diseases, such Alzheimer's, Parkinson's, Transmissible Spongiform Encephalopathies, Diabetes Type II and various systemic amyloidosis. The central event in these diseases is the accumulation of a misfolded, ß-sheet rich aggregated form of a naturally expressed protein. In vitro studies have shown that protein misfolding and aggregation follows a seedingnucleation mechanism similar to the process of crystallization. In this model, the limiting step is the formation of small oligomeric intermediates that act as seeds to catalyze the polymerization process. The seeding-nucleation model provides a rationale and plausible explanation for the infectious nature of prions. Infectivity lies on the capacity of preformed stable misfolded oligomeric proteins to act as a seed to catalyze the misfolding and aggregation process. The mechanism of misfolding and aggregation is similar in all PMD suggesting that misfolded aggregates have an inherent capability to be transmissible. Moreover, it has been shown that oligomeric seeds formed by one protein can accelerate the misfolding and aggregation of another protein, by a process termed cross-seeding. Our current study aims to assess the potential molecular cross-talk among PMD in vivo. For this purpose we inoculated with prions a transgenic mice model of Alzheimer's disease (tg2576) that develops typical amyloid plaques over time. 45, 303 and 365 days old transgenic and wild type mice were inoculated intraperitoneally with RML prions. We found significant diminution in prion incubation periods for tg2576 mice compared to age matched wild type controls. Moreover, a time dependent effect was observed, where the shorter incubation period was observed in animals containing larger number of amyloid plaques. Inoculation of tg2576-RML prions into wild type mice showed incubation periods similar to the original infectious material, suggesting that strains characteristics are maintained. In vitro data showed cross-seeding aggregation between PrPSc and Aß. Our findings suggest an interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second perhaps more prevalent disease. http://www.prion2007.com/pdf/Prion%2...0Abstracts.pdf CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007 http://cjdmadcowbaseoct2007.blogspot.com/ Transmissible Spongiform Encephalopathy UPDATE USA OCTOBER 2007 http://www.phxnews.com/fullstory.php?article=53128 October 2007 Update on Feed Enforcement Activities to Limit the Spread of BSE http://www.phxnews.com/fullstory.php?article=53149 TSS |
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03-22-2008, 01:26 PM | #15 | ||
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Original Paper
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease Laura Debatina, Johannes Strefferb, Markus Geissenc, Jakob Matschkec, Adriano Aguzzia, Markus Glatzela, c aInstitute of Neuropathology, and bDivision of Psychiatry Research, University Hospital Zurich, Zurich, Switzerland; cInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Address of Corresponding Author Neurodegenerative Dis (DOI: 10.1159/000121389) ---------------------------------------------------------------------------- ---- Key Words Sporadic Creutzfeldt-Jakob disease Alzheimer's disease Deposition of -amyloid Prion protein ---------------------------------------------------------------------------- ---- Abstract Background: Alzheimer's disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, -amyloid (A), which deposits in AD, and the abnormal form of the prion protein, PrPSc, which deposits in sCJD. Methods: We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrPSc and A morphologically, biochemically and genetically and correlated these findings to clinical data. Results: sCJD-diseased individuals with abundant deposits of A present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrPSc in the cerebellum. Conclusion: The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of A and PrPSc in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of A and PrPSc in a subgroup of sCJD patients. Copyright © 2008 S. Karger AG, Basel ---------------------------------------------------------------------------- ---- Author Contacts Markus Glatzel Institute of Neuropathology, University Medical Center Hamburg-Eppendorf Martinistrasse 52, DE-20246 Hamburg (Germany) Tel. +49 40 42 803 2218, Fax +49 40 42 803 4929 E-Mail m.glatzel@uke.uni-hamburg.de http://content.karger.com/produktedb...file=000121389 Singeltary, Sr et al. JAMA.2001; 285: 733-734. Diagnosis and Reporting of Creutzfeldt-Jakob Disease Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings. To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally. Terry S. Singeltary, Sr Bacliff, Tex 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT http://jama.ama-assn.org/cgi/content...urcetype=HWCIT see my full text on Alzheimers and CJD blog here ; http://betaamyloidcjd.blogspot.com/2...n-of-beta.html TSS |
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