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I Alafuzoff

Publications and source records attributed to I Alafuzoff.

At least 19 recordsLinked to original sources
PubMed2006

How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

Brain↗
PubMed2006

Cerebroretinal microangiopathy with calcifications and cysts.

BACKGROUND: Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation. METHODS: We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively. RESULTS: Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen. CONCLUSIONS: Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.

Adolescent↗
PubMed2004

Preoperative clinical evaluation, outline of surgical technique and outcome in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

Electroencephalography↗
PubMed2004

Polymorphisms in neprilysin gene affect the risk of Alzheimer's disease in Finnish patients.

OBJECTIVES: Neprilysin (NEP) is an amyloid beta-peptide (Abeta) degrading enzyme expressed in the brain, and accumulation of Abeta is the neuropathological hallmark in Alzheimer's disease (AD). In this study we investigated whether polymorphisms in the NEP gene have an effect on the risk for AD. METHODS: The frequencies of seven single nucleotide polymorphisms (SNPs) and apolipoprotein E (APOE) were assessed in 390 AD patients and 468 cognitively healthy controls. Genotypes of the study groups were compared using binary logistic regression analysis. Haplotype frequencies of the SNPs were estimated from genotype data. RESULTS: Two SNPs, rs989692 and rs3736187, had significantly different allelic and genotypic frequencies (uncorrected p = 0.01) between the AD and the control subjects and haplotype analysis showed significant association between AD and NEP polymorphisms. CONCLUSION: Taken together, these findings suggest that polymorphisms in the NEP gene increase risk for AD and support a potential role for NEP in AD.

Aged↗
PubMed2003

Brain biopsy prior to treatment of Alzheimer's disease.

A cortical biopsy was analyzed using immunohistochemical methodology in a total of 213 patients with suspected normal pressure hydrocephalus (NPH). Normal intracranial pressure (ICP) was registered in 121 (43 %) of patients with suspected NPH. The incidence of Alzheimer's disease (AD) related lesions was quite high, since 38 % of all subjects displayed beta-amyloid (betaA4) aggregates and in 8 % of subjects paired helical filament-tau (PHF-tau) pathology was noted. The AD associated pathologies were more common in subjects with normal than elevated ICP. Of the 121 subjects with NPH, 16 (13 %) had subclinical, histopathologically verified AD and a further 40 subjects (33 %) could be considered to be at high risk to develop AD. Pharmacological treatment trials of AD should be carried out on subjects with evident brain pathology (betaA4 aggregates or PHF-tau pathology) especially during the early stage of the disease, i.e., the subclinical stage. For this purpose a simple cortical biopsy with a low risk of complication would represent a diagnostic "method" of choice.

Aged↗
PubMed2002

Five-year outcome of normal pressure hydrocephalus with or without a shunt: predictive value of the clinical signs, neuropsychological evaluation and infusion test.

BACKGROUND: Between 1993-1995, 51 patients under 75 years of age with clinical symptoms and CT-based diagnosis of normal pressure hydrocephalus were investigated prospectively in order to clarify the value of neuropsychological tests, clinical symptoms and signs and infusion test in the differential diagnosis and prediction of outcome in normal pressure hydrocephalus. METHODS: Patients had a thorough neurological examination, and neuropsychological evaluation. A 24-hour intraventricular ICP-measurement, infusion test, neurophysiological investigations and MRI study were performed, and a cortical biopsy was obtained. The ICP measurement defined the need for a shunt. All 51 patients were re-examined three and twelve months later. The final follow-up was accomplished five years postoperatively. FINDINGS: 25 of the patients needed a shunt operation. One year after a shunt placement 72% of these patients had a good recovery concerning activities of daily living, 58% benefited in their urinary incontinence and 57% walked better. During the 5 years of follow-up 8 patients with shunt and 9 without shunt had died. Positive effect of shunting remained. Only one neuropsychological test, recognition of words test, distinguishes the patients with the need for a shunt. Simple mini mental examination test was not different in those who improved. In the postoperative follow-up patients with shunt showed no change in neuropsychological tests even if they were subjectively better. The infusion test was of no value in diagnosing NPH. The 16 patients with Alzheimer's disease did worse after one year than those without pathological changes, but the mortality was not increased. INTERPRETATION: Specific neuropsychological tests are of little value in diagnosing NPH. Mini-Mental status examination was neither of value in diagnosing NPH nor in prediction of the outcome. In this study the infusion test did not improve diagnostic accuracy of NPH, but shunt placement relieves urinary incontinence and walking disability in patients with increased ICP. The patients with positive Alzheimer diagnosis on biopsy did not improve.

Aged↗
PubMed2002

Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease.

Seladin-1 is a gene recently shown to be down-regulated in brain regions selectively degenerated in Alzheimer's disease. The sequence of seladin-1 shares similarities with flavin-adenine-dinucleotide-dependent oxidoreductases and it has been found to protect cells from apoptotic cell death. In this work, we show that the transcription of seladin-1 is selectively down-regulated in the brain areas affected in Alzheimer's disease. The down-regulation in seladin-1 transcription was associated with hyperphosphorylated tau seen as linkage to immunohistochemically detected paired helical filament tau, neuritic plaques and neurofibrillary tangles. In contrast, no association was found between seladin-1 transcription and beta-amyloid deposition when analyzing human samples or tissue from transgenic animals. Furthermore, the relative transcription of seladin-1 was found to fluctuate during aging in the transgenic mouse model of Alzheimer's disease. The fluctuation was enhanced by Alzheimer's disease causing mutations in presenilin-1 and amyloid precursor protein genes. Finally, seladin-1 transcription was found to be up-regulated in mouse N2a cells induced to undergo apoptosis with okadaic acid. The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer's disease and this down-regulation is associated with the hyperphosphorylation of tau protein.

Aged↗
PubMed2002

Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation.

Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are two major histopathological lesions in Alzheimer's disease (AD). Although their aetiological relationship is unclear, both NFTs and dystrophic neurites of NPs display immunoreactivity for ubiquitin. This suggests that dysfunction in ubiquitin-mediated proteolysis and the resulting accumulation of ubiquitin-conjugated proteins may contribute to the origination of dystrophic neurites and NFTs. We recently discovered a novel constituent of neuropathological protein aggregates, ubiquitin-binding protein p62, with evidence that the accumulation of ubiquitin-conjugated proteins and p62 into cytoplasmic inclusions might be interconnected. In the present work we examined in detail the role of p62 in AD-type pathology, i.e. NFTs, NPs and neuropil threads. Using immunohistochemistry for p62, ubiquitin and hyperphosphorylated tau, we analysed parietal cortical samples of 15 clinicopathologically verified AD cases and nine nondemented aged subjects with abundant NPs. We found that p62 immunoreactivity appears early during neurofibrillary pathogenesis and is invariably and stably present in NFTs. In contrast, p62 was absent or barely detectable in neuropil threads. Furthermore, NP-associated dystrophic neurites were generally devoid of p62, regardless of their content of hyperphosphorylated tau and/or ubiquitin. The results suggest that early involvement of p62 might be critical in the aggregation of hyperphosphorylated tau into perikaryal aggregates, i.e. NFTs.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Molecular genetic analysis of the alpha-synuclein and the parkin gene in Parkinson's disease in Finland.

Two mutations in the alpha-synuclein gene and various mutations in the parkin gene are associated with familial Parkinson's disease (PD). The present study was performed to analyse if mutations in these genes could be detected in Finnish patients with familial PD. The subjects comprised 22 unrelated patients with familial PD. The molecular genetic analysis consisted of sequence analysis of the non-coding and coding exons of the alpha-synuclein gene and screening of eight point mutations in the parkin gene. In addition, a total of 67 controls and 45 patients with sporadic PD were included in the association analysis on polymorphism of the alpha-synuclein gene. Screened point mutations in the parkin gene were not detected. Sequencing of the coding exons 2-6 of the alpha-synuclein gene did not reveal any mutations or polymorphisms. However, three novel alterations in the T10A7 sequence at the 5' end of the non-coding exon 1' of the alpha-synuclein gene were found. The frequencies of the exon 1' polymorphic genotypes or alleles between familial PD patients and control subjects revealed no statistically significant differences. No association for sporadic PD was observed. The results do not support a role for the alpha-synuclein gene or point mutations of the parkin gene in familial PD in our sample.

Aged↗
PubMed2002

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients.

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

Adult↗
PubMed2001

Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation.

Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD). In this study the activity of POP is evaluated in AD patients and in transgenic mice with substantial deposits of beta-amyloid (Abeta). In AD cases, the POP activity displayed a significant negative correlation with the scores of senile/neuritic plaques and neurofibrillary tangles but not with Abeta-load. The transgenic mice with high levels of Abeta did not have altered POP activity compared to wild type mice. Based on our results, the low POP activity in AD seems to be associated with neuronal degeneration rather than to Abeta accumulation.

Age Factors↗
PubMed2001

Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies.

We examined the immunoreactivity of ubiquitin-binding protein p62 and its association with ubiquitin (Ub), alpha-synuclein, and paired helical filament (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies. Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub noncovalently and is involved in several signalling pathways, making p62 a candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity co-localizes with neuronal and glial Ub-containing inclusions in Alzheimer's disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. This is the first demonstration of a common protein component, apart from Ub, that is present in both PHF-tau and alpha-synuclein inclusions. In both tauo- and synucleinopathies, the staining patterns for p62 and Ub were markedly similar, suggesting that a common mechanism which requires interaction of p62 and Ub contributes to the formation of PHF-tau and alpha-synuclein inclusions.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Auditory event-related potentials differentiate patients with normal pressure hydrocephalus and patients with concomitant Alzheimer's disease verified by brain biopsy.

We studied 51 patients with clinical symptoms and CT findings suggesting normal pressure hydrocephalus (NPH). Tests included head MRI, auditory event-related potentials (ERPs), thorough neuropsychological testing and intraventricular intracranial 24 h pressure recording and infusion testing. A brain biopsy was also obtained to verify a concomitant dementing process (Alzheimer's disease; AD). Patients were divided into subgroups according to the need of shunt and the biopsy findings, and their ERPs were analysed blindly. The present results suggest that non-invasive ERPs aid in the differentiation of pure NPH from NPH with concomitant AD.

Aged↗
PubMed2001

The load and distribution of beta-amyloid in brain tissue of patients with Alzheimer's disease.

Recent findings have underlined the significance of beta-amyloid protein (betaA4) in the etiology of Alzheimer's disease (AD). In 60 patients with AD, the amount of betaA4 deposition, estimated applying immunohistochemical techniques, was shown to be significantly influenced by apolipoprotein E (ApoE) genotype (epsilon4/epsilon4 > epsilon4/x > x/x), by the age at onset (presenile > senile), by the age at death (younger > older patients) and by the duration of the disease (long > short). Morphometric analysis revealed that the betaA4 load was highest in the superficial layer of the cortex and a significant influence on the vertical distribution was seen in females but not in males, in familial but not in sporadic cases and in senile but not in presenile cases. Our findings indicate that not only the load but also the vertical distribution of betaA4 within cortex is influenced by risk factors such as ApoE genotype and gender.

Age of Onset↗
PubMed2001

Alpha-synuclein pathology is highly dependent on the case selection.

Lewy bodies and dystrophic neurites have been considered a common substrate for dementia, but they are also frequently found in the normal elderly population. The primary component of this pathology involves alpha-synuclein. The main objective of the present study was to estimate the prevalence of alpha-synuclein pathology in aged population, and to assess its relative significance in relation to dementia. The study also investigated whether differences could be detected in alpha-synuclein pathology in relation to age, gender or concomitant Alzheimer's pathology. Furthermore, the influence of sampling strategies was analysed. Alpha-synuclein pathology was assessed using immunohistochemistry in well-characterized post-mortem material. The investigation included patients from a longitudinal study of dementia of Alzheimer's type (n = 103, 85% demented), subjects from a prospective longitudinal clinical study of ageing (n = 69, 29% demented), a cohort of consecutive clinical post-mortem cases collected for 1 year (n = 262, 12% demented), a sample of forensic post-mortem cases collected for 6 months (n = 121, 15% demented) and a sample of Brain Bank material (n = 234, 26% demented). Overall, alpha-synuclein pathology was found in 14% of all 774 subjects over 40 years of age, and this percentage varied from 8% to 27% according to sampling strategies. These results indicate that the prevalence of alpha-synuclein pathology clearly depends on the selection of material. Furthermore alpha-synuclein pathology was found in 23% of clinically demented patients and in 11% of non-demented subjects. The load of alpha-synuclein pathology was significantly greater in the demented patients versus non-demented subjects indicating that alpha-synuclein pathology is indeed of importance in the pathogenesis of dementia.

Adult↗