metallothionein and Dementia--Vascular

The concentration of plasma copper, ceruloplasmin (CRP), non-ceruloplasmin-bound Cu (NCBC), and metallothioneins (MTs) were studied as putative biomarkers for neurodegenerative diseases in patients and in their first-degree relatives. We found increased levels of Cu in the plasma of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia (VD) patients, and the increase observed in VD group was linked to the evolution of the disease. CRP was also elevated in response to the inflammatory component of the diseases, however, a correlation with illness progression was only observed in VD patients. The level of MTs is proportional to the evolution of VD. The Cu/CRP and Cu/MTs ratios are both indicative of disease progression for AD patients but not for those with PD or VD. Moreover, there is a correlation between the NCBC levels and the cognitive impairment estimated through the Mini-mental State Examination (MMSE) scale. This dependence is linear for AD and PD patients and non-linear for the VD ones. The relative values of NCBC showed dependence on the disease duration, especially for AD. Copper measurement and the Cu/CRP ratio may be predictive markers of risk for the first-degree relatives of AD patients. We believe that these results are valuable as a reliable clinical tool.

Topics: Adult; Aged; Alzheimer Disease; Biomarkers; Ceruloplasmin; Copper; Dementia, Vascular; Disease Progression; Family; Female; Humans; Linear Models; Male; Metallothionein; Middle Aged; Parkinson Disease; Risk Factors; Time Factors

Binswanger's disease is a subacute form of hypertensive encephalopathy characterized by patchy-confluent myelin loss of the deep hemispheric white matter, associated with marked regressive changes of the oligodendrocytes and variable astroglial reaction. To understand the distribution and the specificity of astrocyte pathology in Binswanger's disease we quantified reactive and degenerating astrocytes in different regions of the deep and subcortical white matter and of the cerebral cortex. Sections of frontal, temporal, parietal, and occipital lobes of 12 histologically proven cases of Binswanger's disease were immunostained with antibodies to glial fibrillary protein (GFAP) and to metallothionein I and II (MT-I-II), markers which specifically identify normal and reactive astrocytes. Control tissues were from 6 elderly patients without neurological diseases. The brains of Binswanger's disease were characterized by few and lightly immunostained astrocytes in the deep white matter, but normal and reactive astrocytes, strongly immunoreactive for GFAP and MT-I-II, were prominent in the subcortical white matter and the cerebral cortex. However, the relative distribution of GFAP positive and MT-I-II positive astrocytes was significantly different between the cerebral cortex and the subcortical white matter, the MT-I-II positive astrocytes being more frequent in the cerebral cortex, and the GFAP positive astrocytes in the subcortical white matter (p < 0.02). The GFAP and MT-I-II expressions in subsets of reactive astrocytes in the cortico-subcortical layers together with regressive astroglial changes in the deep white matter suggest that the dynamic plasticity of astroglia is topographically and biochemically differentiated in vascular dementia of Binswanger type.

Topics: Aged; Aged, 80 and over; Astrocytes; Brain; Cerebral Cortex; Dementia, Vascular; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Male; Metallothionein; Nerve Degeneration; Neuronal Plasticity; Reference Values