myelin-basic-protein and Dementia

Longstanding psychological stress has been associated with increased risk of neurodegenerative disorders, such as dementia and Alzheimer's disease. In a prospective population study of women (n = 81), we tested if midlife stress (mean age 49 years) was associated with late-life biomarkers of neurodegeneration in cerebrospinal fluid (CSF) (mean age 74 years) in linear regression models. It was found that women who report of stress at baseline (n = 20) had higher levels of CSF visinin-like protein-1 (VILIP-1) (age adjusted β = 0.113, p = 0.017) and CSF myelin basic protein (β = 0.060, p = 0.030) compared with women without midlife stress (n = 61). There was also a trend observed for higher CSF neurofilament light (β = 0.133, p = 0.056). In addition, longer periods of stress (i.e., stress at 2-3 midlife examinations) were associated with higher levels of CSF VILIP-1. The results suggest that longstanding stress might be associated with neurodegenerative processes in the brain, as CSF VILIP-1 is an unspecific marker for neuronal injury and CSF myelin basic protein reflects neuroaxonal demyelination.

Topics: Aged; Aging; Alzheimer Disease; Axons; Biomarkers; Brain; Dementia; Demyelinating Diseases; Female; Follow-Up Studies; Humans; Middle Aged; Myelin Basic Protein; Nerve Degeneration; Neurocalcin; Neurodegenerative Diseases; Neurofilament Proteins; Risk; Stress, Psychological; Time Factors

The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.

Topics: Aged; Aged, 80 and over; Dementia; Female; Frontal Lobe; Glutathione Transferase; Humans; Immunohistochemistry; Male; Middle Aged; Myelin Basic Protein; Myelin Sheath; Nerve Degeneration; Nerve Fibers, Myelinated; Oligodendroglia; Regression Analysis; Temporal Lobe

The expression of encephalitogenic peptide (EP), a 68-86 amino acid sequence of guinea pig myelin basic protein (MBP), was investigated in autopsied brains with focal cerebral damage or with diffuse white matter (WM) lesions. EP immunoreactive fibers were distributed in parallel with fibers immunoreactive for amyloid protein precursor (APP), an indicator of WM damages. EP was expressed in the periphery of cerebral infarctions and hematoma in the acute and subacute stages, but was also distributed in diffuse WM lesions due to heterogeneous causes. These data indicate that EP epitopes are exposed specifically in ongoing WM damages, and that the destruction of myelin occurs sporadically in diffuse WM lesions of varying intensity.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Animals; Autopsy; Brain; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Circulation; Dementia; Guinea Pigs; Hematoma; Humans; Myelin Basic Protein; Myelin Sheath; Nerve Fibers; Peptide Fragments

We evaluated 130 consecutive HIV-infected neurologically asymptomatic individuals for intrathecal IgG production and myelin basic protein (MBP) levels. Although 56.7% of immunologically normal and 68.8% of immunocompromised patients had some CSF abnormality, no patient had an abnormal MBP level. The lack of MBP elevation in the CSF of these patients suggests that the production of intrathecal IgG is not related to active demyelination.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Dementia; Demyelinating Diseases; Follow-Up Studies; Humans; Immunoglobulin G; Male; Myelin Basic Protein; Neurologic Examination

The nervous system specific proteins glial fibrillary acidic protein (GFAp), S-100 and myelin basic protein (MBP) were determined in 535 human cerebrospinal fluid (CSF) samples. The level of all three proteins was increased in CSF of patients with nonselective destructive central nervous tissue disease such as encephalitis, cerebrovascular disease or tumoural compression. The increases in GFAp were more constant, making it a better marker of CNS pathology. Increases in MBP in CSF of patients with acute demyelinating disease were confirmed. S-100 did not seem to give more information as GFAp. Isolated increases of GFAp could be demonstrated in patients with dementia (Alzheimer type or multi-infarct dementia) or syringomyelia. Since CNS of these patients is very rich in fibrillary astrocytes, containing large amounts of GFAp, it is suggested that GFAp is to be considered as a specific marker of fibrillary gliosis in CSF and can be used as a diagnostic tool in dementia and syringomyelia.

Topics: Cerebrovascular Disorders; Dementia; Glial Fibrillary Acidic Protein; Humans; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases; Nervous System Neoplasms; Polyradiculoneuropathy; S100 Proteins; Syringomyelia

We previously reported a marked increase of a 20,000 molecular weight (MW) protein, P20, in some neuronal fractions and whole cortical homogenates isolated from affected cortex in Alzheimer disease; P20 comigrated electrophoretically with an unidentified, major 20,000 MW protein present in human neurofilament (NF) fractions. We now report that the 20,000 MW protein is a major constituent of rodent as well as human NF fractions and that it comigrates by one- and two-dimensional gel electrophoresis with purified myelin basic protein (MBP). Peptide mapping and staining with amido black confirmed the identity of the 20,000 MW protein of mammalian NF fractions as MBP. One- and two-dimensional gel electrophoresis of neuronal perikaryal fractions from human cortex indicated that the increased P20 protein in Alzheimer neuronal fractions comigrates with human MBP. Deliberate contamination of cortical samples with adjacent subcortical white matter (i.e., myelin) prior to neuronal separation did not result in an increase of P20 in the neuronal fraction. On the basis of these and additional experiments, we conclude that the increase of a 20,000 MW protein in neuronal fractions and whole homogenates from affected cortex in Alzheimer disease represents MBP of intracortical origin.

Topics: Alzheimer Disease; Animals; Cerebral Cortex; Cytoskeleton; Dementia; Electrophoresis, Polyacrylamide Gel; Humans; Mice; Molecular Weight; Myelin Basic Protein; Myelin Sheath; Neurons; Rats

The number of lymphocytes in the blood sensitized to encephalitogenic factor (EF) is less in multiple sclerosis than it is in general paralysis of the insane. The number appears related to the extent of parenchymatous destruction. The study offers no support for the view that lymphocyte sensitization to EF is of pathogenetic significance in multiple sclerosis.

Topics: Adolescent; Adult; Aged; Child; Dementia; Female; Humans; Lymphocyte Activation; Lymphocytes; Macrophages; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases; Syphilis