Fausto Chionne

Oxidative damage to DNA in lymphocytes from AD patients.

Objective: Several studies show structural and functional alterations in peripheral cells in AD. The purpose of this study was to evaluate oxidative stress in AD lymphocytes. Background: The literature supports the role of reactive oxygen species in the pathogenesis of AD because several markers of oxidative damage have been detected in AD brain. Methods: 8-hydroxy-2′-deoxyguanosine (8OHdG), a marker of oxidative stress in DNA, was measured in lymphocytes of AD patients and healthy aged controls with high-pressure liquid chromatography with electrochemical detection, both at basal condition and after acute oxidative stress with hydrogen peroxide. Results: A significantly higher concentration of 8OHdG in lymphocytes occurred in AD patients compared with controls. In this latter group, 8OHdG increased progressively with age. After acute oxidative stress, levels of formed 8OHdG did not differ between AD patients and controls. Conclusions: Our results support that AD is affected by oxidative stress, detectable not only in the brain but also in peripheral cells; oxidative mechanisms may contribute to the pathogenesis of AD. Additional studies in other neurodegenerative diseases are needed to evaluate these findings.

Tau Protein in Cerebrospinal Fluid: A New Diagnostic and Prognostic Marker in Alzheimer Disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

SERUM ANTI-GFAP AND ANTI-S100 AUTOANTIBODIES IN BRAIN AGING, ALZHEIMER'S DISEASE AND VASCULAR DEMENTIA

Autoantibodies against glial fibrillary acidic protein (GFAP) and S100 protein were measured in sera of patients suffering from vascular dementia (VD), presenile Alzheimers disease (AD), senile Alzheimers disease (SDAT) and aged healthy controls by means of ELISA test. VD and SDAT showed the highest levels of both autoantibodies, AD the lowest. From these results a relationship between autoantibody titers and aging seems possible. Dosage of anti-GFAP and anti-S100 autoantibodies does not appear useful for diagnostic purpose because of the overlap observed among groups. Rather, the presence of these antibodies seems to reflect an alteration of the blood-brain barrier that promotes the access of central nervous system antigens to immunocompetent cells.

Altered mitochondrial membrane fluidity in AD brain.

Oxidative damage on biological membranes has been proposed as a cause of the alterations observed in aging brain and, more severely, in Alzheimers disease (AD). In this study we evaluated membrane fluidity of mitochondria extracted from different areas of normal and AD brains by means of fluorescence polarization technique. AD mitochondria showed a significant reduction of membrane fluidity compared to controls except in cerebellum. This might be caused by a greater lipid peroxidation of biological membranes, as suggested by in vitro experiments we performed to this purpose. From these results the possible role of oxidative stress in AD pathogenesis is supported.

Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimers disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimers disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.

AUTOANTIBODIES AGAINST OXIDIZED LOW‐DENSITY LIPOPROTEINS IN OLDER STROKE PATIENTS

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OXIDATIVE STRESS AND LYMPHOCYTES IN ALZHEIMER DISEASE

Summary Oxidative stress has been involved in the pahtogenesis of different neurodegenerative diseases. Recently high levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG). a sensitive marker of DNA damage, were found in both nuclear and mitochondrial DNA of the brain in Alzheimer disease (AD). In this study we measured 8-OHdG in lymphocyte DNA obtained from AD patients and from agematched controls. The high levels of 8-OHdG found in the lymphocytes of AD patients support the hypothesis that a general imbalance is present in this disease between oxidants and antioxidants.

Diagnosing Alzheimer’s Disease in Very Elderly Patients

OBJECTIVES To describe the Gottfries-Bråne-Steen (GBS) Rating Scale more fully with instruments commonly used for the diagnostic assessment of older patients with cognitive disturbances--the Mini Mental State Examination (MMSE), Hamilton Depression Rating Scale (HDRS), and Global Deterioration Scale (GDS)--and to characterize the specific diagnostic value of the GBS. DESIGN A multicenter study including patients diagnosed with senile dementia of the Alzheimer type (SDAT; age at onset: > 75 years) and age-matched non-demented subjects. SUBJECTS One hundred thirty-eight consecutively referred SDAT patients and 116 non-demented age-matched healthy subjects selected from among relatives of the patients. METHODS The MMSE, GBS and HDRS were used for assessing patients and controls. The GDS was utilized for dementia staging. FINDINGS Principal component analysis carried out on GBS scores yielded three factors explaining 74% of variance: factor 1, general functioning; factor 2, depression, and factor 3, restlessness. The actual composition of these factors was analyzed after computing factor scores for each subject by means of forward selection regressions, each using the MMSE, GDS and HDRS as predictors of scores on a given factor. The best predictors were MMSE and GDS scores for factor 1; HDRS for factor 2, and MMSE for factor 3. A GBS cutoff of 8 (obtained after a quality receiver operating characteristic analysis) best discriminated between demented and non-demented subjects (positive-predictive value: 0.88; negative-predictive value: 0.90). CONCLUSIONS The GBS Rating Scale for dementia can be a useful tool in routine clinical assessment of older subjects with cognitive impairment and distinguishes between demented and non-demented subjects; it gives comprehensive information on functional and psychobehavioral characteristics of demented patients, being composed of factors related to the MMSE and HDRS.