Biomedical subjects

C Duyckaerts

Publications and source records attributed to C Duyckaerts.

At least 19 recordsLinked to original sources

PubMed2006

Valosin-containing protein gene mutations: clinical and neuropathologic features.

BACKGROUND: Hereditary inclusion body myopathy (IBMPFD) with Paget disease of bone (PDB) and frontotemporal dementia (FTD) is a rare multisystem disorder with autosomal dominant inheritance. Recently, missense mutations in the gene encoding valosin-containing protein (VCP) have been found in individuals with IBMPFD. VCP/P97, which exerts a variety of cellular functions, plays a key role in the ubiquitin-proteasome dependent degradation of cytosolic proteins and in the retrotranslocation of misfolded proteins from the endoplasmic reticulum into the cytoplasm. METHODS: The authors describe the clinical features of two kindreds in which VCP R93C and R155C missense mutations segregate and perform a histopathologic examination of brain, muscle, bone, and liver of three subjects harboring the R155C mutation. RESULTS: Frontotemporal dementia was present in 100% of affected subjects in Family F1 and 70% in Family F2, as compared with an average of 30% in previously described IBMPFD families. In contrast, PDB was a more inconstant clinical feature. Biochemical and histopathologic data are consistent with the hypothesis that VCP R155C mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. CONCLUSIONS: VCP mutations are present in two families in which FTD is the most prominent symptom. The histopathologic study performed in patients harboring the R155C mutation supports the hypothesis that this mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. IBMPFD belongs to a class of genetic diseases associated with an alteration of the ubiquitin-proteasome system.

Adenosine Triphosphatases↗

PubMed2006

[Nosology of dementias: the neuropathologist's point of view].

The diagnosis of degenerative dementias heavily relies on the identification of neuronal or glial inclusions. Tauopathy is probably the largest group including Alzheimer and Pick disease, mutation of the tau gene, progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. Lewy bodies, when numerous in the cerebral cortex, are usually associated with the cognitive deficit of Parkinson disease dementia or of dementia with Lewy bodies--both conditions being distinguished by clinical information. The inclusions of the dentate gyrus, only labeled by anti-ubiquitin antibodies, isolate a subgroup of fronto-temporal dementia (FTDu), sometimes familial and sometimes associated with amyotrophic lateral sclerosis. Mutations of the progranulin gene have been recently discovered among a significant proportion of these patients. Neuronal Intermediate Filament Inclusion Disease (NIFID) is a rare, apparently sporadic dementia, characterized by the presence of large inclusions in the cell body of many neurons. These inclusions react with antibodies directed against neurofilaments or against other intermediate filaments (such as alpha-internexin). The diagnostic value of some of these inclusions allowing the classification of the degenerative dementias has been discussed. The link between the inclusions and the pathogenetic mechanism is indeed probably variable. It should however be stressed that whenever their composition has been elucidated, the inclusions have given important clues to the pathogenesis of the disease in which they had been found.

Aged↗

PubMed2004

Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease.

BACKGROUND: Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity. OBJECTIVE: To assess the spectrum of the clinical and neuropathological features in 10 NIFID cases. METHODS: Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted. RESULTS: The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and alpha-internexin. CONCLUSION: NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies.

Adult↗

PubMed2004

Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model.

It has been proposed that Alzheimer disease (AD) is associated with a "disconnection syndrome" due to the gradual loss of morphological and functional integrity of cortico-cortical pathways. This hypothesis derives from indirect neuropathological observations, but definitive evidence that AD primarily targets cortico-cortical networks is still lacking. By means of neuroanatomical anterograde tracing methods, we have investigated, in a murine transgenic model of AD, the impact of the amyloid burden on axonal terminals in different neural systems. Axonal tracings revealed, in accordance with the "disconnection syndrome" hypothesis, that cortico-cortical fibers are significantly disorganized. Terminal fields in local and distant cortical areas contained numerous swollen dystrophic neurites often grouped in grape-like clusters at the plaque periphery. In contrary to fibers of cortical origin, those originating from subcortical brain structures only showed limited signs of degeneration upon reaching their cortical targets. These observations suggest a selective disruption of cortico-cortical connections induced by AD brain pathology.

Alzheimer Disease↗

PubMed2003

Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease.

The protein flotillin-1 is associated with the 'lipid rafts', that is, membrane microdomains that are enriched in cholesterol and sphingolipids. We compared flotillin-1 immunoreactivity in the hippocampus, amygdala and isocortex (Brodmann area 22) of six controls and 13 Alzheimer's disease (AD) cases (10 sporadic and three familial). A diffuse labelling of the neuropil was observed in most of the samples. The intensity of this labelling was not correlated with the density of neurofibrillary tangles (NFT) or of senile plaques. Some neuronal cell bodies were diffusely labelled in patients as in controls. Immunostained granular bodies were found in the cell body of a few neurones. The density of neuronal profiles containing large granular bodies (diameter > or =2 microm) was significantly higher in AD cases and was correlated with the density of NFTs in the three regions that were studied. Sections stained by double immunofluorescence methods and examined with confocal microscopy suggested that flotillin-1 accumulated most often in tangle-bearing neurones (76% of flotillin-1-positive neurones contained a NFT). Flotillin-1 immunoreactivity, even when found in a tangle-bearing neurone, was not colocalized with tau protein indicating that the two proteins were not in close contact and probably in different subcellular compartments. Flotillin-1-positive granular bodies were also found in neurones containing Pin1-positive vesicles but were not colocalized with them. Flotillin-1 immunoreactivity was colocalized with cathepsin D, a lysosomal marker. These data indicate that flotillin-1, a marker of rafts, accumulates in lysosomes of tangle-bearing neurones in the course of AD.

Aged↗

PubMed2003

[Recent neuropathology of parkinsonian syndromes].

The understanding of the molecular mechanisms underlying Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy has made significant progress in the recent years. Lewy body appears to be principally made of alpha-synuclein, a presynaptic protein. It also contains ubiquitin and some components of the proteasome: this suggests that alteration of protein catabolism may be involved in its formation. In favor of this hypothesis, it should be noted that Parkin, a protein that is mutated in autosomal recessive Parkinson disease, is a ubiquitin ligase. Immunohistochemistry has shown that alpha-synuclein accumulates not only in the cell body of the neurones (Lewy body) but also in their processes (Lewy neurites); it has emphasized the severity of the pathology in the nucleus basalis of Meynert, amygdala, CA2-3 sector of the hippocampus and cerebral cortex. Cortical Lewy bodies are not considered any more the marker of dementia with Lewy bodies: they are, indeed, found in true Parkinson disease cases. In progressive supranuclear palsy, 4 repeats tau accumulates in the cytoplasm of neurones and glia. At electron microscopy, the accumulation is made of straight filaments. It involves not only the neurones (where it is the main constituent of the neurofibrillary tangles) but also the glia. Astrocytic tuft is to day considered the morphological marker of progressive supranuclear palsy. Tau protein accumulates in the cell body of the oligodendrocyte as a "coiled body"; the protein is also integrated in the myelin sheath, when the cytoplasm of the oligodendrocyte wraps around the axon. This explains the numerous "threads" that are visible in cases of progressive supranuclear palsy. Striato-nigral degeneration, sporadic olivo-ponto-cerebellar atrophy and primitive orthostatic hypotension are various clinico-pathologic aspects of the same disorder: multiple system atrophy. It is also characterized by a morphological marker: the accumulation of alpha-synuclein in the cytoplasm of glial cells, particularly oligodendrocytes. The term synucleinopathy has been proposed to describe both idiopathic Parkinson disease and multiple system atrophy. The reason explaining the cellular topography of alpha-synuclein accumulation, neuronal in Parkinson disease, glial in multiple system atrophy is still unknown.

Amygdala↗

PubMed2003

[Neuropsychological and scintigraphic aspects of frontotemporal dementia preceding amyotrophic lateral sclerosis].

Between 1993 and 2001, we observed fifteen patients (ten men and five women, mean age 63 years) with frontotemporal dementia (FTD) which preceded signs of amyotrophic lateral sclerosis (ALS) which developed 21 months later. Mean disease duration in the fourteen deceased patients was 38 months. FTD associated with ALS is characterized by rapid course, predominance of disinhibited forms (orbito-basal), presence of aphasia with neologisms, and semantic memory disorders. Performed in all patients, single-photon emission computed tomography demonstrated a bifrontal pattern of low uptake, sometimes associated with low uptake in the anterior temporal region. In one patient, neuropathology revealed neuron atrophy and loss in the frontotemporal region, the anterior horns, and the hypoglossal nucleus. Ubiquitin-positive inclusions were visible in the dentate gyrus of the hippocampus and in the anterior horns. The dementia/ALS association is classically described is uncommon. It belongs to the FTD group since the Lund and Manchester consensus. Approximately 15 p.100 of patient with FTD can be expected to develop ALS. About 250 cases have been reported in the literature, half of them in the Pacific area where the incidence of ALS is high (55/100,000 inhabitants versus 1/100,000 in the rest of the world). Intermediary forms of FTD, semantic dementia, and progressive non-fluent aphasia are discussed since several cases of non-fluent progressive aphasia associated with ALS are reported in the literature. The links between these two degenerative diseases are discussed.

Aged↗

PubMed2003

[Neuropathology of tauopathies and synucleinopathies, and neuroanatomy of sleep disorders: meeting the challenge].

Abnormalities of tau and alpha-synuclein have been described in a variety of neurodegenerative diseases often associated with sleep disorders. Neuropathological descriptions concerning these diseases are rapidly expanding, and they become difficult to summarise. On the other hand, the human neuroanatomy of sleep remains an ill defined issue. Main tauopathies are Alzheimer's disease, progressive supranuclear palsy, cortico-basal degeneration, argyrophilic grain disease, Pick disease and fronto-temporal degeneration with Parkinsonism associated with chromosome 17. In contrast to Alzheimer's disease, where abnormal tau containing cells are mainly neurones, in the other disorders, both neurones and glial cells are affected. The presynaptic protein alpha-synuclein is a major constituent of Lewy-type lesions in Parkinson disease and in dementia with Lewy bodies. Alpha-synuclein is also found in neurones and glia of Multi System Atrophy. This led to group these disorders into the still ill defined group of synucleinopathies. The lesions of tauopathies and synucleinopathies are presented, and their distribution in the most common disorders is described, distinguishing when possible neuronal loss and neuropathological markers. Recent data show that their extension is far larger than previously assumed and that they involve a variety of areas possibly involved in sleep regulation. Sleep disorders have been described in various tauopathies and synucleinopathies. However, no detailed clinico-pathological reports concerning the distribution of affected and spared areas in patients studied by polysomnography are available. Furthermore, the similarities of sleep disorders associated with different diseases, the interindividual variability, the frequently associated disorders, and the difficulties in quantifying neuronal loss make any clinicopathological correlation uncertain. The knowledge of sleep neuroanatomy is mainly based on animal studies. The few data concerning the structures of human brain areas involved in sleep organisation are recalled. Several systems known to be acting in sleep physiology are usually affected by tauopathies and synucleinopathies, but the pattern of their involvement in sleep pathology remains highly conjectural. The neuropathology of sleep disorders in tauopathies and synucleinopathies is a still uncultivated field.

Adult↗

PubMed2002

Alpha-synuclein-immunoreactive deposits in human and animal prion diseases.

Prion related disorders are associated with the accumulation of a misfolded isoform (PrPsc) of the host-encoded prion protein, PrP. There is strong evidence for the involvement of unidentified co-factors in the PrP to PrPsc conversion process. In this study, we show alpha-synuclein-immunoreactive deposits in the central nervous system of various prion diseases (sporadic, iatrogenic and new variant Creutzfeldt-Jakob diseases, and experimental scrapie of hamsters). alpha-Synuclein accumulated close to PrPsc deposits but we did not observe strict colocalization of prion protein and alpha-synuclein immunoreactivities particularly in PrPsc plaques. alpha-Synuclein is thought to be a key player in some neurodegenerative disorders, is able to interact with amyloid structures and has known chaperone-like activities. Our results, in various prion diseases, suggest a role for alpha-synuclein in regulating PrPsc formation.

Animals↗

PubMed2002

Office of Rare Diseases neuropathologic criteria for corticobasal degeneration.

A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis.

Atrophy↗

PubMed2002

[Alzheimer's disease: a public health problem: yes, but a priority?].

Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

Accidents, Traffic↗

PubMed2002

[Neuropathology of the cerebral vessels of centenarians].

Neuropathological study of brain and brain vessels was performed in two series of 12 and 20 centenarians, focusing on the prevalence of small vessel lesions, infarction, Alzheimer's changes and mental status. These are discussed as a function of vascular risk factors. In the first series (12 cases), there was no correlation between the severity of small vessel lesions: hyalinosis (12/12), mineralisation (10/12), amyloid angiopathy (9/12), vascular risk factors (high blood pressure or diabetes), Alzheimer's lesions. However, there was a tendency for an association between amyloid angiopathy and high density of neurofibrillary tangles. In the second series (20 cases), small infarcts and lacunes were found in 9/20 cases, neurofibrillary tangles and diffuse deposits of A beta peptide were constant, senile plaques were very frequent (19/20). Five patients were demented (one vascular dementia, one Alzheimer dementia, and 3 mixed dementias). These data indicate that: 1) Lesions of the walls of small cerebral vessels do not seem linked to the vascular risk factors observed at the end of the life of centenarians. 2) Cerebral infarcts and lacunes are frequent in these patients, and are responsible, at least in part, for a high proportion of the cognitive dysfunctions. The study of larger series is needed for a better understanding of relationships between vascular and degenerative lesions in the oldest old.

Aged↗

PubMed2001

Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant polyglutamine disorder presenting with progressive cerebellar ataxia and blindness. The molecular mechanisms underlying the selective neuronal death typical of SCA7 are unknown. We have established SCA7 cell culture models in HEK293 and SH-SY5Y cells, in order to analyse the effects of overexpression of the mutant ataxin-7 protein. The cells readily formed anti-ataxin-7 positive, fibrillar inclusions and small, nuclear electron dense structures. We have compared the inclusions in cells expressing mutant ataxin-7 and in human SCA7 brain tissue. There were consistent signs of ongoing abnormal protein folding, including the recruitment of heat-shock proteins and proteasome subunits. Occasionally, sequestered transcription factors were found. Activated caspase-3 was recruited into the inclusions in both the cell models and human SCA7 brain and its expression was upregulated in cortical neurones, suggesting that it may play a role in the disease process. Finally, on the ultrastructural level, there were signs of autophagy and nuclear indentations, indicative of a major stress response in cells expressing mutant ataxin-7.

Adult↗

PubMed2001

Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat in the coding region of the SCA7 gene. The disease primarily affects the cerebellum and the retina, but also many other central nervous system (CNS) structures as the disease progresses. Ataxin-7, encoded by the SCA7 gene, is a protein of unknown function expressed in many tissues including the CNS. In normal brain, ataxin-7 is found in the cytoplasm and/or nucleus of neurons, but in SCA7 brain ataxin-7 accumulates in intranuclear inclusions. Ataxin-7 is expressed ubiquitously, but mutation leads to neuronal death in only certain areas of the brain. This selective pattern of degeneration might be explained by interaction with a partner that is specifically expressed in vulnerable cells. We used a two-hybrid approach to screen a human retina cDNA library for ataxin-7-binding proteins, and isolated R85, a splice variant of Cbl-associated protein (CAP). R85 and CAP are generated by alternative splicing of the gene SH3P12 which we localized on chromosome 10q23-q24. The interaction between ataxin-7 and the SH3P12 gene products (SH3P12GPs) was confirmed by pull-down and co-immunoprecipitation. SH3P12GPs are expressed in Purkinje cells in the cerebellum. Ataxin-7 colocalizes with full-length R85 (R85FL) in co-transfected Cos-7 cells and with one of the SH3P12GPs in neuronal intranuclear inclusions in brain from a SCA7 patient. We propose that this interaction is part of a physiological pathway related to the function or turnover of ataxin-7. Its role in the pathophysiological process of SCA7 disease is discussed.

Alternative Splicing↗

PubMed2001

Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions.

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are responsible for colon cancer in familial adenomatous polyposis coli and in many sporadic colorectal tumors. The product of the APC gene is also essential for normal development and is expressed in the adult brain. We have investigated the immunocytochemical localization of APC in the temporal cortex and hippocampus of normal human brain, in Alzheimer's disease (AD) and in several other neuropathological conditions. APC was expressed in neuronal cell bodies and dendrites both in control subjects and in patients with different diseases. In addition, a high APC expression was observed in a proportion of fibrillary and glial fibrillary acidic protein-positive astrocytes in AD. Furthermore, in AD the proportion of APC-positive astrocytes was higher in astrocytes associated with beta-amyloid (Abeta) deposits in senile plaques than in astrocytes not associated to Abeta deposits. APC-positive astrocytes were also observed in control cases, in diffuse Lewy body disease, in Creutzfeldt-Jacob disease, in HIV encephalitis and around cerebral infarcts. Tumoral astrocytes in pilocytic astrocytoma and in glioblastoma were also strongly APC positive. APC was not detected in cultured astroglial cells. These results indicate that APC expression is upregulated in astrocytes following their activation by several types of pathological insults and is a newly identified molecular characteristic of the reactive phenotype of astrocytes, possibly related to the control of cell proliferation. In addition, it also suggests that Abeta, and/or the inflammatory process associated with Abeta deposits, is responsible for a preferential increase of APC expression in astrocytes in AD.

Adenomatous Polyposis Coli Protein↗

PubMed2001

FE65 in Alzheimer's disease: neuronal distribution and association with neurofibrillary tangles.

FE65, a protein expressed in the nervous system, has the ability to bind the C-terminal domain of the amyloid precursor protein. This suggests a role for FE65 in the pathogenesis of Alzheimer's disease (AD). The present study was conducted to find out if the distribution of FE65 immunoreactivity was affected during the course of AD, and to determine the degree of co-localization of FE65 with other proteins known to be involved in AD. Single immunoperoxidase-labeling experiments, conducted on six sporadic AD patients and six nondemented age-matched controls, showed that the proportion of volume occupied by FE65 immunoreactivity was not modified in the isocortex of AD patients. However, in hippocampal area CA4, increased FE65 immunoreactivity seemed to be associated with the severity of the disease. Double-immunofluorescent labeling did not show any clear co-localization of FE65 with the amyloid precursor protein. FE65 immunoreactivity was also absent from focal and diffuse deposits of the beta-amyloid peptide. Unexpectedly double labeling experiments showed a co-localization of FE65 and tau proteins in intracellular tangles. Ultrastructural observations confirmed that FE65 was associated with paired helical filaments.

Aged↗

PubMed2001

[Associations of patients and tissue banks].

Research dealing with tissue is more important to day than ever. Techniques of molecular genetics have indeed permitted the identification of a large number of new proteins that have now to be localised in the tissue and in the cell, in health and disease. This step has to be made in order to elaborate the adequate animal models in which new therapeutics can be tested. In France, however, human tissue samples have become difficult to obtain. Many factors contributed to this situation. Autopsies are now exceptionally performed. Doctors feel confident in their diagnosis and express rarely the need to control it. Families are opposed to post mortem more strongly than before, especially when the reasons for performing it can not be explained before the death of the patient. French law now makes the explicit consent of the patient mandatory before any research. This practically limits all post mortem investigations to those that had been planned before death. The possibility of giving tissue post mortem to allow research has to be publicised, particularly by associations of patients. The organisation that should manage to collect and store the samples at a large scale and over the whole country is lacking. Its structure is still discussed: should it be supported by the state itself, by private funding, possibly by the associations of patients themselves? Patients Associations are ready to play a crucial role: they realised that the present system was inefficient, they are presently trying to organise tissue banks; they will finally have to explain to their members why they should care for research, how they could help and how they will have to accept the absence of immediate spectacular results.

France↗

PubMed2000

Dementia with Lewy bodies in a neuropathologic series of suspected Creutzfeldt-Jakob disease.

Discriminating Creutzfeldt-Jakob disease (CJD) from dementia with Lewy bodies (DLB) may be clinically difficult to achieve. The authors describe 10 patients with DLB initially referred to the French Network of Human Spongiform Encephalopathies as having suspected CJD. In a series of 465 autopsied cases, DLB ranked second among degenerative alternative diagnoses to CJD. The authors analyzed the factors that contributed to misleading the diagnosis, and suggest that the detection of 14-3-3 protein in CSF may be useful to distinguish CJD from DLB.

Aged↗