Biomedical subjects

P Fredman

Publications and source records attributed to P Fredman.

At least 37 records · Page 2Linked to original sources

PubMed2000

Monoclonal anti-GD3 antibodies selectively inhibit the proliferation of human malignant glioma cells in vitro.

The frequently occurring alteration of ganglioside expression in tumor cells has been implicated to play a role in the uncontrolled growth of these cells; antibodies to such gangliosides might affect tumor cell growth. We have studied the effect of IgM monoclonal antibodies to two glioma-associated gangliosides, GD3 and GM2, on cell proliferation of four human glioma cell lines and one renal tumor cell line. Of the two anti-ganglioside antibodies tested, only the anti-GD3 antibody resulted in a significant (p<0.005) inhibition of cell proliferation as measured by thymidine incorporation and Brd-U labeling, after 24h incubation. The effect was not dependent on any serum factor and no increased cell death was observed. All cell lines contained higher or similar amounts of GM2 than GD3, and both antigens were shown to be expressed on the cell surface and accessible to antibodies. The selective effect of anti-GD3 antibodies as contrasted to the inactivity of anti-GM2 antibodies suggests a possible role for ganglioside GD3 in tumor cell proliferation.

Antibodies, Monoclonal↗

PubMed2000

The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: possible involvement in insulin trafficking.

In previous studies we have shown that sulfatide (galactosylceramide-3-O-sulfate), in various species, is present in the insulin-producing cells in pancreatic islets of Langerhans. In this study the synthesis of sulfatide in the islets has been investigated by pulse chase labeling at varying glucose levels and in the presence or absence of the glycosphingolipid synthesis inhibitory agents, Brefeldin A, fumonisin B1 and chloroquine and the distribution of sulfatide by immune-electronmicroscopy. The data showed that (1) sulfatide was produced in islets of Langerhans, (2) the main pathway for synthesis was through recycling involving partial degradation in the lysosome, and that (3) high glucose levels, although not primarily reflected in an increased synthesis of sulfatide, lead to an increased expression of mRNA for the UDP-galactose:ceramide galactosyltransferase, producing the immediate precursor of sulfatide. Furthermore, mass spectrometry analyses revealed a high proportion of short chain fatty acids, C16:0 (50%) and no hydroxylated forms and thus special physicochemical properties, indicating important differences between pancreatic and brain/neural sulfatide. Immune electron microscopy revealed an intracellular expression of sulfatide in the secretory granules, the Golgi network and the lysosomes of the islets. These results indicate that sulfatide follows the same intracellular route as insulin and suggest a functional association between these molecules. We have raised the hypothesis that sulfatide possibly plays a role in the trafficking of insulin in the islets of Langerhans in rat pancreas.

Animals↗

PubMed2000

CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.

OBJECTIVES: To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features. METHODS: CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH. RESULTS: The CSF sulfatide concentration was markedly increased in patients with SAE (mean 766, range 300-3800 nmol/l) compared with patients with NPH (mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP in CSF were higher in patients with SAE than in patients with NPH. The patients with NPH with cerebrovascular aetiology had higher sulfatide concentrations and a poorer outcome after shunt surgery than patients with NPH with other aetiologies. CONCLUSIONS: The pathogenesis of the white matter changes in NPH and SAE is different and ischaemic white matter changes can be a part of the NPH state. The markedly increased CSF sulfatide concentrations in patients with SAE indicate ongoing demyelination as an important pathophysiological feature of SAE. The CSF sulfatide concentration distinguished between patients with SAE and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker.

Adult↗

PubMed1999

Recovery of severe sciatica.

STUDY DESIGN: A prospective study of patients with acute severe sciatica. OBJECTIVES: To 1) describe the characteristics of patients with acute severe sciatica and the agreement among different diagnostic tests, 2) describe overall recovery during 1 year in terms of perceived disability, and pain, and 3) explore acute-phase predictors of failure to recover at 1 year. SUMMARY OF BACKGROUND DATA: The development of imaging techniques has been very impressive during recent decades. However, different authors have highlighted the prevalence of abnormal images among asymptomatic subjects. These findings increase the difficulty of interpreting the results from the diagnostic techniques used with each individual patient. Furthermore, other clinical and biopsychosocial variables need to be explored for their associations with recovery or failure to recover. This study aimed to explore those associations. METHODS: Consecutive patients admitted to the hospital for conservative management of severe acute sciatica were eligible for inclusion in the study. Patients were evaluated at admission, discharge, and 3, 6, and 12 months. All the visits included a standardized clinical examination and the completion of questionnaires that included items on demographics, pain, perceived disability, and quality of life. Imaging and blood samples were collected at the first visit, and an electromyogram was taken for sciatica lasting at least 3 weeks. RESULTS: The study included 82 consecutive patients (66% men) with a mean age of 43 +/- 10.3 years. The mean intensity of pain, on a visual analog scale of 0 to 100 (VAS) at Visit 1, was 73. The straight leg raising test was positive in 78% of the patients, with a mean value of 59 degrees +/- 18 degrees. The contralateral straight leg raising test was positive in 20% of the patients. Imaging was positive for disc herniation in 74% and electromyogram was positive in 62% of cases. These two diagnostic tests showed a good to excellent total agreement (58-87%) with the straight leg raising tests and the presence of radiating pain below the knee. The recovery of clinical symptoms and signs was observed mainly within the first 3 months. However, clinical recovery and perceived recovery was not complete in most cases. CONCLUSIONS: In most cases, there was good to excellent agreement among the different diagnostic tests. None of the tests was predictive of recovery. The presence of blood antibodies against 3'LM1 (IgM + IgG) and GD1a (IgM) was significantly associated (P < 0.023) with neurologic symptoms and signs. However, the meaning of these antibodies remains unclear. Only a minority of the patients (29%) had fully recovered after 12 months. Within the 1-year follow-up, one third of the patients had surgery.

Adult↗

PubMed1999

In vitro production of cytokines is influenced by sulfatide and its precursor galactosylceramide.

Effects of sulfatide and its precursor galactosylceramide (gal-cer) on the kinetics of production of cytokines were studied. In human mononuclear leucocytes, gal-cer but not sulfatide induced significantly increased amounts of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF) mRNA. In phytohemagglutinin-stimulated cultures, gal-cer increased the levels of IL-1beta and IL-6 mRNA and secreted IL-1beta and IL-6, while sulfatide decreased the amounts of IL-6 mRNA and secreted IL-6. Gal-cer also increased TNF secretion. In lipopolysaccharide-stimulated cells, sulfatide but not gal-cer decreased the secretion of IL-1beta and IL-10, a potent suppressor of production of many cytokines. Thus, sulfatide and gal-cer affect cytokine production differently, most likely at the level of gene expression. This may have implications in diseases where inflammatory cytokines play a pathogenic role.

Adult↗

PubMed1999

High levels in serum, but no signs of intrathecal synthesis of anti-sulfatide antibodies in HIV-1 infected individuals with or without central nervous system complications.

Myelin degeneration is commonly found in the central nervous system (CNS) of individuals infected with human immunodeficiency virus type 1 (HIV-1), especially in patients with HIV-1-associated dementia. We analysed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1 infected individuals for the presence of antibodies directed against sulfatide, the major acidic glycosphingolipid in myelin. Nine of the patients had CNS complications, including 3 with HIV-1-associated dementia, and 16 had no neurological symptoms. Elevated titres of anti-sulfatide antibodies were found in serum from 24/25 HIV-1-infected individuals but in none of them in the CSF. Although the vast majority of HIV-1-infected individuals harbour autoantibodies directed against sulfatide in serum, the lack of detectable intrathecal production indicates that anti-sulfatide antibodies are not a major component in the pathogenesis of CNS myelin damage in HIV-1 infection.

AIDS Dementia Complex↗

PubMed1999

Inhibition of insulin-specific autoreactive T-cells by sulphatide which is variably expressed in beta cells.

AIMS/HYPOTHESIS: Sulphatide and insulin are present in the secretory granules and at the surface of beta cells in islets of Langerhans. Insulin autoantibodies and T-cell reactivity against insulin exist during the development of Type I (insulin-dependent) diabetes during which active beta cells may be more vulnerable than passive. Our aims were to examine the presence of sulphatide in active and passive beta cells and to clarify whether sulphatide influences the direct autoimmunity against insulin. METHODS: We incubated rat islets in 2.8, 11.0 or 20.0 mmol/l glucose for 24 h and did an electron microscopic evaluation after labelling with a specific anti-sulphatide monoclonal antibody. The reactivity of an insulin-specific T-cell clone isolated from a patient with Type I diabetes, was examined using insulin or insulin B-chain (B11-27) peptide incubated together with sulphatide. RESULTS: We detected lower amounts of sulphatide per insulin secretory granule in active compared with passive beta cells (p = 0.003). The presence of sulphatide in vitro at doses of 43-8.3 micromol/l resulted in greatly reduced proliferation (median 3.4 % of control value, p = 0. 0004) of the insulin-specific T-cell clone. No inhibition was found using the precursor of sulphatide, galactosylceramide, or GM1. Sulphatide did not reduce non-aspecific proliferation (induced by phorbol myristate acetate plus anti-CD3) or specific proliferation induced by insulin peptide. CONCLUSION/INTERPRETATION: These results imply that sulphatide possibly affect processing of the insulin molecule. Sulphatide which has been reported to interfere with phagosome-lysosome fusion, conceivably interacts with insulin. We hypothesize a (patho)physiological role of sulphatide, variably expressed in beta cells, by reducing the antigenicity of insulin. [Diabetologia (1999) 42: 1212-1218]

Animals↗

PubMed1999

Expression of the GM1-species, [NeuN]-GM1, in a case of human glioma.

Altered glycosylation is a common feature in tumors of various kind and particular interest has been focused on the expression of tumor-associated gangliosides. We have previously identified some human glioma-associated gangliosides and in this study yet another, not previously described, ganglioside has been isolated. The ganglioside was prepared from human glioma tissue taken at autopsy. The new ganglioside bound cholera-toxin B-subunit and its structure was confirmed by fast atom bombardment-mass spectrometry to be NeuN-GM1 (II3NeuNH2-GgOse4Cer). In the dissected tumor specimen, the concentration of NeuN-GM1 was 0.1 micromol/g wet weight and accounted for approximately 20% of the monosialoganglioside fraction. Normal human brain tissue specimens (n = 10) did not contain detectable (>0.5 nmol/g wet weight of tissue) amounts of NeuN-GM1, indicating that this ganglioside might be associated with human glioma. However, none of the 17 other tumour specimens reveal any detectable amounts of this ganglioside. In conclusion, NeuN GM1 is a glioma-associated ganglioside but its exceptional expression limits its relevance as a molecule involved in general tumor biology.

Brain↗

PubMed1999

Identification of defensins in human lymphocyte nuclei.

The cell nucleus plays an essential role in all aspects of cell function and regulation. Most of the nuclear proteins/peptides are synthesized in the cytoplasm and transported into the nucleus through the nuclear pore complexes. The nuclear proteins/peptides conjugate with each other and interact in transcriptional activation/inactivation. Several of the high molecular mass transcription factors (> 30 kDa) have been identified and characterized. However, the information on the low molecular mass proteins/peptides of the nucleus is limited. We have investigated these low molecular mass proteins/peptides from the nucleus of human peripheral blood lymphocytes using reversed-phase high-performance liquid chromatography (RP-HPLC). The HPLC fractions were further analysed by matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, electrospray ionization time of flight (ESI-TOF) mass spectrometry and electrospray ionization fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry for mass determination. Using this combination of mass spectrometry techniques and microsequence analysis, we have shown that human lymphocyte nuclei contain defensins, a mixture of human neutrophil granule peptide 1, 2 and 3.

Amino Acid Sequence↗

PubMed1998

Increased cerebrospinal fluid ganglioside GD3 concentrations as a marker of microglial activation in HIV type 1 infection.

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the infectious course. The predominant, productively infected cell type within the CNS is the microglial cell. We have analyzed the cerebrospinal fluid (CSF) levels of the ganglioside GD3, a microglia/macrophage and astrocyte marker, in 22 HIV-1-infected individuals at different stages of the disease, and in 44 age-matched HIV-negative, healthy controls. To distinguish between microglial/macrophage and astroglial involvement, the GD3 levels were compared with CSF levels of the glial fibrillary acidic protein (GFAp), which is expressed exclusively in astrocytes. A significantly higher mean CSF concentration of GD3 was found in HIV-1-infected patients compared to controls (56.7 and 40.1 nmol/L, respectively, p < 0.001). Seven of 22 HIV-1-infected patients had increased CSF levels of GD3 (above mean + 2 SD in controls), all but one of these had normal levels of GFAp, indicating a microglial activation or proliferation as the major source of the increased GD3 levels.

Adult↗

PubMed1998

The role of antiglycolipid antibodies in neurological disorders.

Glycolipids have been shown to be antigens for circulating antibodies in autoimmune processes affecting the nervous system like neuropathy associated with IgM paraproteinemia, Guillain Barré syndrome (GBS), multifocal neuropathy, and variants thereof. The antibody titers, the Ig-classes, and the antibody specificity vary between studies and disease groups. The immunogens are in general unknown. However, GBS is often associated with an infection with Campylobacter jejuni, which expresses a lipopolysaccharide structure similar to the carbohydrate epitopes in sialic acid containing glycolipids and gangliosides and thus a potential primary antigen for antiganglioside antibodies. The antiglycolipid specificity will most likely reflect the primary antigen carbohydrate epitopes, which also determine the target cell or tissue structure and the pathology. These factors might add to the inconsistent results obtained and that have led to the question: Are antiglycolipid antibodies of any clinical significance?

Animals↗

PubMed1998

Intracellular sulfatide expression in a subpopulation of astrocytes in primary cultures.

A highly specific antibody against sulfatide, a myelin-associated glycolipid, has been investigated using indirect double immunocytochemistry in rat primary astroglial cultures from cerebral cortex. Sulfatide was expressed in a selected subpopulation of astrocytes (2-3%) and was found to be exclusively located intracellularly. The sulfatide-positive cells appeared in two different morphologies: flat and stellate. Immunolabeling of the astroglial cultures showed that sulfatide always co-existed with GFAP or S-100, and in some cells with GD3 (flat 90% and stellate 50%) or A2B5 (1%) antibody. The sulfatide-positive cells did not bind the O1 antibody, which is used as a marker for oligodendrocytes. Glial cultures from other regions and mixed cultures, with both neurons and glial cells, were examined and showed similar results. Biochemical analysis by TLC-ELISA verified the presence of sulfatide in the astroglial culture and showed decreasing amounts of sulfatide with days in vitro; 0.05 nmol/mg protein at day 10 and 0.01 nmol/mg protein at day 17. This analysis also showed that neither sulpholactosylceramide nor seminolipid was present, each of which also has affinity for the sulfatide antibody. This selective and intracellular expression encourages further identification of the astrocytes expressing sulfatide and the biological role of sulfatide in these cells.

Animals↗

PubMed1998

A new procedure for determining ganglioside GD3 a potential glial cell activation marker in cerebrospinal fluid.

Increased amounts of ganglioside GD3 [II3 (NeuAc)2-LacCer], associated with reactive gliosis, have been documented in a variety of neurodegenerative disorders. GD3 expression has also been reported in microglial cells, not only during development but also in reactive states, where the glial activation is considered to be part of the repair process. It is important to find markers in cerebrospinal fluid that will enable us to identify damage and register changes in pathological processes within the brain. A sensitive and practically applicable method for determination of GD3 ganglioside in cerebrospinal fluid has been developed. The procedure, which includes extraction, purification on silica gel and thin-layer enzyme-linked immunostaining, also allows determination of sulphatide, a marker of demyelinating processes, in the same portion of CSF. The method has been applied to CSF samples from 101 normal individuals aged 2-83 years. The GD3 concentration was found to be significantly correlated to age and reflecting the concentrations within the brain. GD3 ganglioside analysis by means of this method might be useful for studying glial changes during brain maturation as well as in brain disorders.

Adolescent↗

PubMed1998

Sphingolipids and cell signalling.

The sphingolipid storage disorders constitute a group of inherited metabolic disorders in which the structure of the stored sphingolipid and the corresponding genetic defect have been established. However, the pathological mechanism(s) behind the disorders has not been fully elucidated. Sphingolipids are known to be recognition molecules involved in intercell communication and altered expression might lead to dyscommunication. The impaired degradation and lysosomal accumulation of specific sphingolipids might influence the metabolism of other molecules and/or intracellular transport, which in turn might alter the distribution of these molecules. However, the progress of these diseases indicates that additional factors, besides the stored sphingolipid itself, might be involved. During the last decade, several sphingolipids have emerged as active participants in intracellular signalling processes such as growth control and apoptosis. Particular interest focused on the sphingolipid metabolites, ceramide and sphingosine, as potential mediators in intracellular events and an altered presence of these metabolites in sphingolipidoses cannot be ruled out. Some sphingolipids have been found to influence cytokine release and thereby might induce immunological processes, which are known to exist in at least one of the sphingolipidoses--Gaucher disease. These processes might already have a pathogenic effect during early development, before significant storage has occurred.

Animals↗

PubMed1998

Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.

Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.

Adolescent↗

PubMed1998

A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality.

OBJECTIVES: To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. METHODS: A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. RESULTS: At the age of 85, carriers of the apoE epsilon4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE epsilon4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE epsilon4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE epsilon4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE epsilon4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The epsilon2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05). CONCLUSIONS: Neither the apoE epsilon4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia substantially.

Aged↗

PubMed1998

A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer's disease and vascular dementia.

We investigated blood-brain barrier (BBB) function in relation to Alzheimer's disease (AD) and vascular dementia (VAD) in the very elderly. Sixty-five 85-year-old persons from a population-based sample were followed for 3 years; 29 were demented at age 85 (13 with AD, 14 with VAD, and 2 with other dementias), 7 developed dementia during follow-up, and 29 remained nondemented. CSF/serum albumin ratio was used as as a measure of BBB function. Dementia was defined according to the DSM-III-R, AD according to the NINCDS-ADRDA criteria, and VAD according to the NINDS-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria. Mean CSF/serum albumin ratio was higher in all dementias (8.5 +/- 4.3; p = 0.007) and in the subtypes AD (8.9 +/- 5.3; p = 0.046) and VAD (8.7 +/- 3.5; p = 0.002) than in nondemented individuals (versus 6.5 +/- 2.0), but it was not related to dementia severity. Nondemented women at age 85 (n = 3) who developed dementia during the follow-up had a higher CSF/serum albumin ratio than those not developing dementia (10.4 +/- 2.0 versus 6.0 +/- 1.9; p = 0.007). Nondemented individuals lacking the apolipoprotein E epsilon3 allele (n = 4) had a higher CSF/serum albumin ratio (9.3 +/- 0.8 versus 6.6 +/- 2.1; p = 0.029) than other individuals. A relative BBB dysfunction is associated with both AD and VAD among very elderly individuals. This finding is possibly found early in the disease before the onset of clinical dementia.

Aged↗

PubMed1997

Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions.

OBJECTIVE: To further elucidate the pathogenetic role of apolipoprotein E (Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid (CSF) levels of Apo E in 85-year-old subjects with dementia disorders. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Population-based sample of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia [VAD]; and 2, other types of dementia) and 35 nondemented individuals. MAIN OUTCOME MEASURES: Cerebrospinal fluid levels of Apo E, Apo E polymorphism, and brain atrophy and white matter lesions (WMLs) measured by computed tomography (CT) of the brain. Dementia was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria; AD, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; and VAD, National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neuroscience criteria. RESULTS: The mean (+/- SD) CSF levels of Apo E were lower in the AD (2.6 +/- 1.5 mg/L; P < .02) and VAD groups (2.5 +/- 0.9 mg/L; P < .002) than in the nondemented group (3.8 +/- 1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with increasing severity of dementia and with increasing temporal cortical and central frontal atrophy. In nondemented individuals, CSF levels of Apo E decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo E were not influenced by the Apo E4 isoform. CONCLUSIONS: Whether our finding of an association between low CSF levels of Apo E and dementia disorders (both degenerative, such as AD, and vascular, such as VAD) is related to the pathogenesis of these disorders or is a secondary consequence of the disease process remains to be established. Although statistical correlations do not give direct evidence of causal relations, the correlations between CSF level of Apo E and severity of dementia and cortical atrophy suggest that CSF level of Apo E follows the disease process.

Aged↗