Altered amyloid β-protein precursor processing in brains of patients with neuronal ceroid lipofuscinosis

Wisniewski, Krystyna E.; Kida, E; Gordon-Majszak, W; Saitoh, Tsunao

doi:10.1016/0304-3940(90)90176-a

Cited by 25 publications

(8 citation statements)

References 12 publications

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“…Our previous investigations had shown strong immunoreactivity of NCL brain with mAbs 4G8 directed against amino acid residues 17-24 of A4, especially in the late infantile, juvenile, and adult forms, that were seen at the EM level in the lysosomes, mainly in the fingerprint and cur-vilinear profiles [Wisniewski et al, 1990b;Kitaguchi et al, 19901. On the basis of these data, we carried out the immunocytochemical studies using antibodies directed against other domains of APP and showed variability in the immunoreactivity at the light and EM levels, indicating different origins.…”

Section: Discussionmentioning

confidence: 97%

Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: Review of data and observations

et al. 1992

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We reviewed the clinical and pathological data on 319 neuronal ceroid lipofuscinosis (NCL) cases to determine the degree of variability within the different forms and among and within families. Thirty-six cases (11.3%) were the infantile form; 116 cases (36.3%), late infantile; 163 cases (51.1%), juvenile; and four cases (1.3%), the adult form (Kufs disease). Clinical variability was found in all forms studied, but was most striking in the juvenile and late infantile forms of NCL. The expected initial findings of seizures, dementia, blindness, or motor impairment were evident in 255 cases (80%), and rarer, less typical initial neurological symptoms were seen mainly in the 64 cases (20%) of the juvenile form: behavior abnormalities (18/64), psychoses (12/64), neuropathy (2/64), involuntary movements (15/64), ataxia (9/64). Six juvenile and two adult cases had no detectable impairment of vision. All 319 NCL cases had skin or conjunctive biopsies or buffy coats that showed the characteristic ultrastructural abnormalities of NCL. Variability was evident in 16.7% in that a combination of fingerprint, curvilinear, and membranous profile inclusion bodies was observed in storage lysosomes, although one type of inclusion was distinctly predominant for each form. Postmortem examination of brains of 19 NCL cases (three with the infantile form, six with the late infantile form, nine with the juvenile form, and one with the adult form) revealed characteristic changes. Sixteen of the 19 NCL brains (84%) showed pathological variability in that they contained more than one kind of characteristic inclusion body in the neuronal lysosomal storage compartment. In all 19 NCL brains, small amounts of aging lipofuscin were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 97%

Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: Review of data and observations

et al. 1992

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“…In the three post-mortem cases, pathological studies (light and ultrastructural) of the brain were performed. The methods (histologieal, histochemical, immunocytochemical, and ultrastructural) used for brain, skin punch biopsy and/or buffy coat studies were described previously (28,30,31,32,35).…”

Section: Methodsmentioning

confidence: 99%

“…ease (1,3,15,19,21,22,36,37,38). A number of studies have suggested that in NCL, there may be adefeet in glycoprotein metabolism (5,7,13,27,28,29), as weIl as protein abnormalities (8,12,17,18,31).…”

Section: Introductionmentioning

confidence: 99%

New Subform of the Late Infantile Form of Neuronal Ceroid Lipofuscinosis

Wisniewski

Kida²,

Connell³

et al. 1993

Neuropediatrics

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Clinicopathological studies of a series of nine children with a new subform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is between 2.5-3.5 years of age with initial neurological symptoms of abnormal motor skills caused by cerebellar and extrapyramidal signs. Soon after dementia, myoclonic seizures are followed. Visual impairment is more clearly seen after the age of 5 or 6 years. The ultrastructural studies of the skin and/or buffy coat showed abundant lysosomal storage of curvilinear profiles, rarely intermixed with fingerprint profiles. The MRI of the head performed in seven cases, showed initially enlargement of the ventricles that is secondary to basal ganglia atrophy and presence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased signals of T2-weighted imaging in the periventricular areas of the fronto-parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). The MRI in Cases 7 and 9 was not performed. The electrophysiological abnormalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generalized brain atrophy and unique type of neuronal cytoplasmic inclusion body in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebral cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Klüver-Barrera method.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Subunit C of mitochondrial ATP synthase is one of the stored peptides but unlike CLN2, where 80% of the stored proteolipid consists of subunit C of mitochondrial ATP synthetase, this protein is only one of several proteolipids stored in CLN3. Wisniewski et al [] identified abnormal processing of amyloid beta‐protein precursor in brains from patients with CLN3.…”

Section: The Genetic Classification Of the Ncl'smentioning

confidence: 99%

The neuronal ceroid‐lipofuscinoses

Bennett

Rakheja

2013

Dev Disabil Res Revs

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The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in remaining neurons. Neurons appear to die because of increased rates of apoptosis and altered autophagy. Ten genes have been identified so far that result in an NCL (CLN1-10). The most common forms are CLN1, CLN2, and CLN3, which were previously known as Infantile, Late-Infantile, and Juvenile NCL's, respectively. CLN1 and CLN2 result from mutations in soluble lysosomal enzymes palmitoyl-protein thioesterase (PPT) and tripeptidyl peptidase 1 (TPP1), which can be measured in white blood cells for clinical diagnosis. Molecular diagnostic testing is routinely available for CLN1, CLN2, and CLN3. Sequencing of other NCL genes may be required to establish a diagnosis when the common forms are ruled out. The pathogenesis of NCL neuronal loss resulting from loss of function of any of the NCL gene products remains unknown and no treatment options are presently available.

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Altered amyloid β-protein precursor processing in brains of patients with neuronal ceroid lipofuscinosis

Cited by 25 publications

References 12 publications

Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: Review of data and observations

Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: Review of data and observations

New Subform of the Late Infantile Form of Neuronal Ceroid Lipofuscinosis

The neuronal ceroid‐lipofuscinoses

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