Hornerin deposits in neuronal intranuclear inclusion disease: direct identification of proteins with compositionally biased regions in inclusions.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder, characterized by the presence of eosinophilic inclusions (NIIs) within nuclei of central and peripheral nervous system cells. This study aims to identify the components of NIIs, which have been difficult to analyze directly due to their insolubility. In order to establish a method to directly identify the components of NIIs, we first analyzed the huntingtin inclusion-rich fraction obtained from the brains of Huntington disease model mice.

Hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (HGA) is an autosomally dominantly inherited form of systemic amyloidosis, characterized mainly by cranial and sensory peripheral neuropathy, corneal lattice dystrophy, and cutis laxa. HGA, originally reported from Finland and now increasingly from other countries in Europe, North and South America, and Asia, may still be underdiagnosed worldwide. It is the first and so-far only known disorder caused by a gelsolin gene defect, namely a G654A or G654T mutation.

The neuronal ceroid-lipofuscinoses: a historical introduction.

The neuronal ceroid-lipofuscinoses (Batten disease) collectively constitute one of the most common groups of inherited childhood onset neurodegenerative disorders, and have also been identified in many domestic and laboratory animals. The group of human neuronal ceroid-lipofuscinoses currently comprises 14 genetically distinct disorders, mostly characterised by progressive mental, motor and visual deterioration with onset in childhood or adolescence. Abnormal autofluorescent, electron-dense granules accumulate in the cytoplasm of nerve cells, and this storage process is associated with selective destruction and loss of neurons in the brain and retina.

[Hereditary gelsolin amyloidosis--40 years of Meretoja disease].

Hereditary gelsolin amyloidosis is an autosomally dominantly inherited systemic disease, first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1 000, and the disease has subsequently been found in many other countries as well. It's typical initial manifestation is lattice corneal dystrophy, detected at biomicroscopic examination of the eye by the age of 25 to 30 years, followed by slowly progressing cranial neuropathy with bilateral facial palsy, polyneuropathy and generalized cutis laxa.

The neuronal ceroid-lipofuscinoses: from past to present.

The neuronal ceroid-lipofuscinoses (NCLs) are inherited lysosomal storage diseases and constitute the most common group of children's progressive encephalopathies. Most childhood forms of NCL are clinically characterized by progressive loss of vision as well as mental and motor deterioration, epileptic seizures, and premature death, while the rare adult forms are dominated by dementia. All forms of NCL share common pathomorphological features.

Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis.

Congenital neuronal ceroid-lipofuscinosis (NCL) is a devastating inherited neurodegenerative disorder of unknown metabolic basis. Eight patients with this rare disorder, all with similar clinical and neuropathological findings, have been reported, and here we describe two further patients. Previously, we showed that a mutation in the cathepsin D gene causes congenital NCL in sheep.

Incidence of dementia in very elderly individuals: a clinical, neuropathological and molecular genetic study.

Aims: To evaluate the effect of medical record use on figures for the incidence of dementia and the effect of apolipoprotein E (APOE) polymorphism on this incidence and neuropathologically defined Alzheimer's disease (AD) in very elderly individuals.

Methods: Cognitive functions were examined in a cohort of 328 (92% of the very elderly people of a town participated in this study) nondemented Finnish elderly individuals 85 years of age or more in 1991. The examination was repeated in survivors in 1994, 1996, 1999 and 2001.

Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a two-stage study.

Genetic linkage studies have provided evidence for a late-onset Alzheimer's disease (AD) susceptibility locus on chromosome 21q. We have tested, in a two-stage association study, whether allelic or haplotype variation of the beta-amyloid cleaving enzyme-2 (BACE2) locus on chromosome 21q affects the risk of late-onset AD. In stage-1, an unselected population-based sample of Finns aged 85 years or over (n=515) was analysed.

Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses.

Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material.

Cutis laxa in hereditary gelsolin amyloidosis.

Background: Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age-associated systemic disease with global distribution, caused by a G654A or G654T gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this disease. However, only few data on the dermatological involvement are available, and the pathogenesis of this amyloidosis-associated form of cutis laxa has remained unknown.

Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation.

The neuronal ceroid-lipofuscinoses (NCLs) are recessively inherited lysosomal storage diseases, currently classified into 8 forms (CLN1-CLN8). Collectively, the NCLs constitute the most common group of progressive encephalopathies of childhood, and present with visual impairment, psychomotor deterioration and severe seizures. Despite recent identification of the underlying disease genes, the mechanisms leading to neurodegeneration and epilepsy in the NCLs remain poorly understood.

High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3.

The neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5-T 1H magnetic resonance (MR) and ex vivo 14.

Neuropsychological functions in variant Alzheimer's disease with spastic paraparesis.

Few data exist on the effects of specific Alzheimer's disease (AD)-related mutations on cognitive function. We present neuropsychological test results in eight members of a large kindred with variant Alzheimer's disease (VarAD) due to a deletion of the presenilin 1 (PS-1) gene, encompassing exon 9. The disease was neuropathologically characterized by the presence of large, unusual, "cotton wool" plaques (CWP).

The normal population distribution of PRNP codon 129 polymorphism.

Objectives: The common prion protein gene (PRNP) codon 129 polymorphism modifies the susceptibility to and the phenotype of prion diseases. However, no truly representative normal population-based data, or data stratified according to age or gender are available on the distribution of this polymorphism.

Material And Methods: Allelic variation of codon 129 in three Finnish populations representing different age groups, and among Finnish, British and Irish blood donors were examined.

DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), Nasu-Hakola disease, is a globally distributed recessively inherited disease. PLOSL is characterized by cystic bone lesions, osteoporotic features, and loss of white matter in the brain leading to spontaneous bone fractures and profound presenile dementia. We have earlier characterized the molecular genetic background of PLOSL by identifying mutations in two genes, DAP12 and TREM2.

The neuronal ceroid-lipofuscinoses.

The neuronal ceroid-lipofuscinoses (NCLs) collectively constitute the most common group of neurodegenerative diseases in childhood and usually show an autosomal recessive mode of inheritance. Despite varying ages of onset and clinical course characterized in most instances by progressive mental and motor deterioration, blindness, epileptic seizures, and premature death, all forms of NCL show unifying histopathological features. There is accumulation of autofluorescent, periodic acid-Schiff-, and Sudan black B-positive granules that are resistant to lipid solvents in the cytoplasm of most nerve cells and.

Status epilepticus induces changes in the expression and localization of endogenous palmitoyl-protein thioesterase 1.

Kainic acid (KA)-induced experimental epilepsy, a model of excitotoxicity, leads to selective neuronal death and synaptic restructuring. We used this model to investigate the effects of neuronal hyperactivation on palmitoyl-protein thioesterase 1 (PPT1), the deficiency of which causes drastic neurodegeneration. Immunological stainings showed that epileptic seizures in adult rats led to a progressive and remarkable increase of PPT1 in limbic areas of the brain.