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Elisabet Englund

Publications and source records attributed to Elisabet Englund.

At least 19 recordsLinked to original sources
PubMed2006

Cholinergic neuronal defect without cell loss in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.

Animals↗
PubMed2006

Alzheimer's disease (AD) with and without white matter pathology-clinical identification of concurrent cardiovascular disorders.

Clinical vascular features, either as manifest vascular disease or as cardiovascular risk factors were compared in AD with and without neuropathological white matter disease (WMD). The aim of the study was to investigate whether the presence of WMD and the severity of either AD pathology or WMD were associated with different cardiovascular profiles. A total of 44 AD cases were retrospectively studied. All the cases were neuropathologically diagnosed as AD with WMD (n=22) and as AD without WMD (n=22), respectively. The patients' medical records were studied with regard to their medical history and to somatic and neurological findings including arrhythmia, congestive heart failure, angina, myocardial infarctions, signs of TIA/stroke, diabetes mellitus, and blood pressure abnormalities, such as hypertension and orthostatic hypotension. In AD-WMD, hypertension, orthostatic hypotension as well as dizziness/unsteadiness were significantly more common than in AD without WMD. Cardiovascular symptoms were more frequent in AD-WMD than in the other group, though the difference did not reach statistical significance. Hypothetically, abnormal and unstable blood pressure levels underlie recurrent cerebral hypoperfusion, which may in turn leave room for the development of WMD. Furthermore, dizziness/unsteadiness may be a symptom reflecting the presence of WMD.

Aged↗
PubMed2006

Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia.

Cerebral amyloid angiopathy (CAA) caused by deposition of amyloid beta (Abeta) peptides in the cerebrovasculature, involves degeneration of normal vascular components and increases the risk of infarction and cerebral hemorrhage. Accumulating evidence suggests that sporadic CAA is also a significant contributor to cognitive decline and dementia in the elderly. However, the mechanisms by which CAA arises are poorly understood. While neuronal sources of Abeta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process. To better understand CAA mechanisms in dementia, we assessed the frontal cortex of 62 consecutive cases of Alzheimer's disease (AD), vascular dementia (VaD), and mixed dementia (MD) using immunohistochemistry with antibodies to Abeta, smooth muscle actin and the carboxyl-terminal peptides to detect Abeta(40) and Abeta(42). While vascular Abeta deposition was invariably associated with smooth muscle degeneration as indicated by absence of smooth muscle cell actin reactivity, VaD/MD cases exhibited markedly more vascular Abeta(42) deposits and smooth muscle actin loss compared to AD cases with similar degrees of CAA and Abeta(40) deposition. This suggests that distinct mechanisms are responsible for the differential deposition of Abeta in CAA associated with AD and that associated with ischemic/cerebrovascular disease. It is plausible that experimental studies on the effects of cerebrovascular disease on Abeta production and elimination will yield important clues on the pathogenesis of CAA.

Actins↗
PubMed2006

Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia.

BACKGROUND AND PURPOSE: Vascular dementia (VaD) has occasionally been associated with cerebral amyloid angiopathy (CAA), but the prevalence and significance of this counterintuitive relationship are poorly known. Therefore, we investigated the presence and characteristics of CAA in brains of VaD cases. METHODS: We examined temporal and parietal regions of the cerebral cortex of 26 consecutive VaD cases from the Lund Longitudinal Dementia Study. We carried out immunohistochemistry and routine stainings, determined Apolipoprotein E (ApoE) genotypes, and obtained clinical characteristics on the studied group for retrospective analysis. RESULTS: CAA was marked in eight out of 26 cases, and correlated strongly with the presence of cortical microinfarcts, both in the temporal lobe and in the parietal lobe. Based on comparisons with eight age-matched VaD cases without CAA, the clinical records suggested that VaD cases with CAA as a group exhibited less pronounced neurological symptoms. A clear contribution of the ApoE genotype could not be identified. CONCLUSIONS: Based on a combination of the clinical and pathological data, we suggest that microinfarcts in the cerebral cortex associated with severe CAA may be the primary pathological substrate in a significant proportion of VaD cases. Future studies should be undertaken to confirm or dismiss the hypothesis that these cases exhibit a different symptom profile than VaD cases without CAA.

Aged, 80 and over↗
PubMed2006

White matter mapping in Alzheimer's disease: A neuropathological study.

White matter disease (WMD) with pervasive non-focal subtotal tissue loss is frequently seen in Alzheimer's disease (AD) upon neuropathological examination. Although WMD has varying effects on AD symptoms, accurate clinical detection is difficult due partly to scarcity of correlative structural imaging and histopathological studies. Neuropathological studies of WMD severity and distribution have been conducted earlier using semi-quantitative methods. A technique for quantifying WMD objectively in large white matter areas, based on optical density (OD) measurements on images of scanned whole-brain sections, was developed and was validated using conventional microscopic assessment. Altogether, 16 AD cases with concomitant WMD (AD-WMD) and 9 cases of AD without WMD (AD-only) were analysed. The OD values correlated significantly with the neuropathological severity of WMD and were significantly lower in AD-WMD than in AD-only in frontal, frontoparietal, temporal and parietal white matter but not in the occipital white matter, the frontal OD difference being greatest. Useful baseline information on WMD distribution in AD to relate to in vivo imaging results was obtained.

Aged↗
PubMed2006

Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.

Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.

Adrenergic Agonists↗
PubMed2005

Cell type- and region-dependent coxsackie adenovirus receptor expression in the central nervous system.

Model systems have shown that adenoviral vector mediated transient gene expression can potentially be applied for the treatment of brain tumours, neurodegenerative diseases and brain injuries. Most studies utilized adenovirus serotype 5 (Ad5) based vectors, which as adhesion molecules require the coxsackie adenovirus receptor (CAR) as a critical determinant for cellular infection. In this report, we have systematically characterized CAR expression in the adult human central nervous system (CNS) by using immunohistochemistry. A total of 85 specimens from various CNS regions were investigated for CAR expression in a cell type-dependent context. The most marked staining positivity was found in the choroid plexus and the pituitary gland. The neocortex had scattered positive neurons, while the white matter was mainly negative. We need to consider the possible adverse effects and the possible damage caused by adenoviral gene therapy if the virus-vector also binds to normal brain cells.

Adult↗
PubMed2005

Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease--a neuropathological study.

BACKGROUND: White matter disease (WMD) is frequently seen in Alzheimer's disease (AD) at neuropathological examination. It is defined as a subtotal tissue loss with a reduction of myelin, axons and oligodendrocytes as well as astrocytosis. Studies quantitatively defining the myelin loss in AD are scarce. The aim was to develop a method that could provide numerical values of myelin density in AD. The purpose was to compare the myelin contents in increasing grades of pathology of WMD, with age and cortical AD pathology as well as in different regions of the brain in AD. MATERIAL AND METHODS: Sixteen cases with AD and concomitant WMD were investigated with an in-house developed image analysis technique to determine the myelin attenuation with optical density (OD) in frontoparietal, parietal, temporal and occipital white matter on whole brain coronal sections stained for myelin with Luxol Fast Blue (LFB). The OD values in LFB were compared grouped according to Haematoxylin/Eosin (HE) evaluated mild, moderate and severe WMD or normal tissue. The OD values were also correlated with age and cortical AD pathology and compared between the different studied white matter regions. RESULTS: Increasing severity of WMD was associated with a statistically significant OD reduction. No correlation was seen between age and OD or overall cortical AD pathology. The OD values were significantly lower in frontoparietal-compared to occipital white matter. CONCLUSIONS: Myelin loss in AD with WMD is a marked morphologic component of the disease and it is possible to determine the reduction objectively in neuropathological specimens with quantitative measures. This may be of use for clinical diagnostics including brain imaging.

Age Factors↗
PubMed2005

The heterogeneity of frontotemporal dementia with regard to initial symptoms, qEEG and neuropathology.

OBJECTIVES/METHODS: Ten patients with neuropathologically verified frontotemporal dementia (FTD) were analysed for neuropathological features in relation to first presenting and dominating symptoms, age at onset and duration of dementia, as well as to EEG/quantitative EEG. RESULTS: Cases with a late onset (> 65 years) initially presented language disturbances, while the early onset group (< 65 years) showed predominantly behavioural symptoms and mood alterations as early features. The late onset group presented combined cortical-subcortical degeneration including white matter pathology, while early onset cases showed pathology predominantly in the cortex. EEG was normal in the late onset group, while it was mildly and variably abnormal in those with early onset. CONCLUSIONS: Within this small sample of clinical and neuropathological FTD, cases with late vs early onset differed with respect to initial symptoms, EEG findings and regional distribution of brain pathology.

Age of Onset↗
PubMed2004

[Therapeutic hypothermia after cardiac arrest. A cold intravenous fluid, a cooling helmet and a cooling blanket efficiently reduce body temperature].

Two controlled randomized trials have shown that mild systemic hypothermia after cardiac arrest is beneficial for neurological outcome and one of the studies shows an improved survival rate. A pilot study was performed to evaluate a model of induced hypothermia after cardiac arrest, using cold intravenous fluids and surface cooling with a cold helmet and a coldwater blanket (Thermowrap). The main purpose was to evaluate our cooling method regarding efficacy, safety and usability. Five unconscious patients after cardiac arrest were treated with induced hypothermia of whom three survived with good recovery to six-month follow up. Two patients died in the ICU without regaining consciousness. There were no adverse events during treatment. We conclude that our method is reasonably fast compared to other published methods, it is easy to perform and it offers a good temperature control during cooling and rewarming. Routines for evaluating prognosis and neurological outcome after cardiac arrest and hypothermia treatment need to be revised.

Bedding and Linens↗
PubMed2004

Severe cerebral amyloid angiopathy characterizes an underestimated variant of vascular dementia.

Cerebral amyloid angiopathy (CAA) is a frequent finding on neuropathological examination of patients with Alzheimer's disease (AD). A recent study from our laboratory showed that CAA also frequently occurred in vascular dementia with additional mild Alzheimer encephalopathy (VaD-ae, i.e. Alzheimer pathology that does not fulfill criteria for AD). Because CAA is associated with cerebral hemorrhages and infarctions, it is of significant interest to confirm or dismiss the hypothesis that CAA contributes clinically in the many patients that present with VaD-ae. Therefore, we examined entire temporal lobes of 11 VaD-ae cases and 11 age-matched AD cases with Abeta immunohistochemistry. Six of 11 VaD-ae cases had severe CAA, more extensive than in any AD case. There was a trend toward more cortical infarctions in this group, indicating that CAA in VaD may be of clinical importance and an underestimated cause of dementia.

Aged↗
PubMed2004

MRI with diffusion tensor imaging post-mortem at 3.0 T in a patient with frontotemporal dementia.

The formalin-fixed brain of a patient with clinically diagnosed frontotemporal dementia (FTD) was examined post-mortem using magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) at 3.0 T. Frontotemporal atrophy as well as bilateral frontal white matter abnormalities were seen. The white matter changes were slightly more extensive on DTI than on conventional MRI. Correlation with histopathology of the corresponding regions revealed typical frontal lobe degeneration of non-Alzheimer type, with mild frontotemporal degeneration in the outer cortical layers and a moderate frontal white matter gliosis with demyelination. Post-mortem MRI/DTI with histopathologic correlation will enhance our understanding of the basis of white matter changes observed in dementia patients and may improve the in vivo MRI/DTI diagnostic assessment in FTD.

Aged↗
PubMed2004

Negative neurofilament light and tau immunostaining in frontotemporal dementia.

We investigated the immunohistochemical stainability of phosphorylated tau and the light (NFL), intermediate (NFM), and heavy (NFH) neurofilament proteins in postmortem brain tissue from 8 patients with frontotemporal dementia (FTD), for comparison with 6 patients with Alzheimer's disease (AD), and 6 normal controls. In the FTD group, the neuropathological diagnosis was pure frontal-lobe degeneration of non-Alzheimer type (FLD) in 6 cases and in the remaining 2 cases mixed FLD-AD and frontal AD, respectively. The staining for tau was negative in 5 of the FLD cases and faintly positive in 1, but positive in all AD cases. The antibodies against NFM and NFH stained positive in FLD, AD, and controls, whereas the staining for NFL was negative in all FLD cases and positive in 1 AD case and in the controls. These findings regarding NFL and tau staining may be useful in the differential diagnosis of FLD and AD.

Aged↗
PubMed2003

Brain tissue microarrays in dementia research: white matter microvascular pathology in Alzheimer's disease.

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non-neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well-characterized materials (e.g. in quantitative mapping of white matter changes).

Aged↗
PubMed2002

Neuropathology of white matter lesions in vascular cognitive impairment.

The white matter is an important locus for tissue damage in vascular cognitive impairment and white matter lesions often dominate over gray matter changes. The spectrum of ischemic white matter lesions histopathologically represents focal and diffuse lesions, the most common form being the combination of both, in varying proportions. In the combined pathology, the diffuse lesion represents a gradient zone of damage towards surrounding normal tissue and may hold over 200 times the volume of an identified focal lesion, the lacunar infarct. Pathogenetically, the focal lesion results from the acute reaction to regional ischemia, while the diffuse white matter lesion represents the adjustment to altered perfusional and physiological conditions within the tissue.

Aged↗
PubMed2002

Caudate nucleus dopamine d(2) receptors in vascular dementia.

Caudate nucleus dopamine (DA) D(2) receptors were studied in patients with vascular dementia (VaD) and in a control group using [(3)H]raclopride as a radioligand. There was no significant difference in the number of DA D(2) receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D(2) receptors in Alzheimer's disease and Parkinson's disease.

Aged↗