Biomedical subjects

K Blennow

Publications and source records attributed to K Blennow.

189 records · Page 11Linked to original sources

PubMedDate not supplied

Glial fibrillary acidic protein in the cerebrospinal fluid of patients with dementia.

Glial fibrillary acidic protein (GFAP) is the structural protein of the astroglial intermediate filament that forms the morphological basis of astrogliosis. In the present study, GFAP concentrations in cerebrospinal fluid were measured in patients with various dementia diseases. A significant correlation between GFAP and age was found both in the total dementia group and in the controls. Covariance analysis with GFAP as dependent variable and age and albumin ratio as covariates followed by multiple group comparisons showed that, with regard to GFAP levels, the controls (n = 39) differed significantly from the patients with vascular dementia (n = 20; p < 0.05), senile dementia of the Alzheimer type (n = 29; p < 0.05), and 'pure' Alzheimer's disease (n = 8; p < 0.05), but not from those with frontal lobe dementia (n = 5).

Adult↗

PubMedDate not supplied

Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform.

Apolipoprotein E (apoE) has been suggested to play a role in regenerative processes in the brain after trauma, and also in the pathogenesis of Alzheimer's disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF-apoE was decreased in all of EAD (1.8 +/- 1.1 mg/l; p < 0.0005), LAD (2.5 +/- 0.9 mg/l; p < 0.0005), VAD (2.3 +/- 1.4 mg/l; P < 0.0005) and FLD (3.0 +/- 1.3 mg/l; p < 0.05) compared to the control group (5.7 +/- 4.0 mg/l). Since apoE4 has been found to bind to beta/A4-amyloid, and AD patients homozygous for apoE4 to have higher number of senile plaques than apoE3 homozygotes, we also examined the relation between CSF-apoE and apoE alleles. However, CSF-apoE did not significantly differ between patients with different apoE isoforms. Our findings support that apoE is involved in the pathogenesis of dementia disorders, both degenerative and vascular, but the CSF-apoE level is not influenced by the apoE isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative disorders, but not in purpose of differential diagnostics between different dementia disorders.

Age of Onset↗

PubMedDate not supplied

Diagnosis of dementias using partial least squares discriminant analysis.

Twenty patients with Alzheimer's disease (AD), 34 with senile dementia of the Alzheimer type (SDAT) and 12 with vascular dementia (VAD) were carefully investigated. The diagnoses were made according to the DSM-III-R criteria and for AD/SDAT also according to the NINCDS-ADRDA criteria. The data set consisted of 29 descriptor variables obtained at the examination, and the data were fitted to a partial least squares model using dummy variables for the response variables (i.e. clinical diagnoses). The distribution of the scores over the descriptor variable space revealed adequate classification regarding all three diagnoses, with some overlap between SDAT and AD and between VAD and SDAT. The study demonstrates a clear difference in symptomatology between AD and SDAT with no influence of age per se or the severity of dementia.

Aged↗

PubMedDate not supplied

Chromogranin A in cerebrospinal fluid: a biochemical marker for synaptic degeneration in Alzheimer's disease?

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value as a biochemical marker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and there was no significant correlation between CSF-CrA and the blood-brain barrier function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum-CrA. These findings suggest that the major portion of CSF-CrA is locally produced within the CNS. There were no significant differences in CSF-CrA between the AD (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups (99.9 +/- 58.9 ng/ml, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml, respectively). However, when the AD group was subdivided into AD type I (n = 12) and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml), p < 0.02, and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0.05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a biochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.

Aged↗

PubMedDate not supplied

Clinical heterogeneity of probable Alzheimer's disease.

When the symptomatology in probable Alzheimer's disease (AD) was studied, two subgroups emerged: one with predominant cortical symptoms of parietal type (AD type I) and another with general cognitive symptoms but absence of or only mild cortical symptoms (AD type II). In AD type I, the age at onset was significantly lower, confusional symptoms and leukoariosis on computerized tomographic scan were less frequent, and the ganglioside GM1 concentration in cerebrospinal fluid was significantly higher than in AD type II. Although the significance of changes in cerebrospinal fluid gangliosides has not been fully elucidated, it is possible that the increase in cerebrospinal fluid GM1 reflects a more severe degeneration of neurons and synapses in AD type I than in AD type II. The relation between symptomatology and leukoariosis suggests that leukoariosis has clinical significance in AD patients. The total results suggest heterogeneity of probable AD. AD type I appears to constitute a classic AD subgroup with memory disturbances and marked cortical symptoms of parietal type, while age-related changes, vascular changes, and leukoariosis may be responsible for the more generalized symptomatology in AD type II.

Aged↗

PubMedDate not supplied

Heterogeneity of vascular dementia: mechanisms and subgroups.

Today, multiple, thromboembolically generated cerebral infarcts are regarded as the main pathogenetic pathway of vascular dementia (VAD), with multi-infarct dementia (MID) as its clinical counterpart. However, taking into account other vascular mechanisms that may influence the brain, such as vessel-wall damage (atherosclerosis, hyalinosis, amyloid angiopathy, or blood-brain barrier dysfunction), cerebrovascular insufficiency (disturbance of systemic circulation, perfusion vulnerability related to the vascular anatomy of the brain, or disturbance of autoregulation), and hyperviscosity, it is evident that MID is not the only VAD category. The diagnosis of MID ought to be reserved for the combination of progressive dementia associated with cerebral ischemic events and evidence of infarction that is mainly associated with the large cerebral arteries. Subcortical white-matter dementia characterized by frontosubcortical symptomatology, white-matter lesions, and small-vessel involvement with or without lacunes/infarcts--a combination of lacunar dementia and Binswanger's disease--appears to be another important VAD disease.

Aged↗

PubMedDate not supplied

The growth-associated protein GAP-43 is increased in the hippocampus and in the gyrus cinguli in schizophrenia.

Schizophrenia is a common and severe psychiatric disorder of unknown etiology. Numerous neuropathological studies have found subtle structural changes in limbic structures, especially medial temporal lobe structures and the gyrus cinguli. To test the hypothesis that synaptic disturbances are involved in the pathogenesis of schizophrenia, we studied the growth-associated protein 43 (GAP-43), a protein localized to presynaptic terminals, suggested to be involved in establishment and remodeling of synaptic connections, in postmortem brain tissue, using quantitative Western blotting immunohistochemistry. The material consisted of brain tissue from 17 schizophrenics (80 +/- 11 yr), diagnosed according to the DSM-III-R criteria, and 20 age-matched controls (75 +/- 13 yr). Quantitative analyses showed increased GAP-43 protein levels in schizophrenic compared to control brains, both in the hippocampus (2.43 +/- 0.78 vs 1.00 +/- 0.29; p < 0.0001) and in the gyrus cinguli (1.52 +/- 0.21 vs 1.00 +/- 0.35; p < 0.0001). Also by immunohistochemistry, increased GAP-43 staining was found in schizophrenic compared with control brains, throughout all layers of the gyrus cinguli and the hippocampus. Anomalous synaptic sprouting and reorganization, with resultant "miswiring," as well as a defect in synaptic pruning have been hypothesized to be pathogenetic factors in schizophrenia. We suggest that a decreased synaptic density, whether caused by disturbed development or damage/degeneration, may elicit a reactive synaptogenesis (reflected by an increase in GAP-43), which may be functional or anomalous. Synaptic pathology in the limbic system may be of importance in the development of psychotic symptoms in schizophrenia.

Aged↗

PubMedDate not supplied

CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease.

With the arrival of effective symptomatic treatments and the promise of drugs that may delay progression, we now need to identify Alzheimer's disease (AD) at an early stage of the disease. To diagnose AD earlier and more accurately, attention has been directed toward peripheral biochemical markers. This article reviews promising potential cerebrospinal fluid (CSF) biomarkers for AD focussing on their role in clinical diagnosis. In particular, two biochemical markers, CSF total tau (t-tau) protein and the 42 amino acid form of beta-amyloid (Abeta42), perform satisfactorily enough to achieve a role in the clinical diagnostic settings of patients with dementia together with the cumulative information from basic clinical work-up, genetic screening, and brain imaging. These CSF markers are particularly useful to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias. In order to discriminate AD from other primary dementia disorders, however, more accurate and specific markers are needed. Preliminary evidence strongly suggests that quantification of tau phosphorylated at specific sites in CSF improves early detection, differential diagnosis, and tracking of disease progression in AD.

Alzheimer Disease↗

PubMedDate not supplied

Cerebrospinal fluid markers of pathogenetic processes in vascular dementia, with special reference to the subcortical subtype.

There is a need for improvement of the diagnosis of vascular dementia (VaD). Today, the clinician has to rely on clinical examination, history, and, possibly, brain imaging to identify cerebrovascular damage and other signs of VaD. The clinical diagnosis of subcortical VaD may be difficult because the clinical manifestation of this disorder is often similar to that of Alzheimer disease. There are also mixed forms of the two disorders. Biochemical diagnostic markers, which reflect the pathogenetic processes in the brain, would add to the accuracy of the diagnosis. There are some interesting candidate markers: the cerebrospinal fluid (CSF)/serum albumin ratio could be used to identify blood-brain barrier damage to the small intracerebral vessels, CSF sulfatide to identify ongoing demyelination of the white matter, CSF neuron-specific enolase to identify ongoing neuronal degeneration, and CSF tau protein and CSF neurofilament light protein to identify ongoing axonal degeneration. None of these potential markers is specific to subcortical VaD, but together and used in conjunction with the conventional diagnostic workup, they may be of diagnostic value.

Alzheimer Disease↗