S28 THIRD INTERNATIONAL CONFERENCE ON ALZHEIMER’S DISEASE

109 A RATIONAL. APPROACH TO TliS STUDY OF BIOCNEMICAL DIAGNOSTIC MARKEBS OF ALZHEIMSB'S DISSASE. Kaj Blennor, Anders Wallin. Departmant of Ps chiatry and Neurochemistr GSteborg, tilnda r I'

University of Hospital, S-431 SO l&lnda , Sweden.

A correct clinical diagnosis of Alaheimer's disease (AD) is of importance both in clinical practice an+ for.scientific studies. nowever, today thp. c+nxal zheimer's is on a rather prmrtlve level, by ray of exclusion,

dar;;sdi;;no::8

markers exist. and no positive biochen+al diagnostic

with "pure" AD.can more readily .be lden$rfxe Data are pre?ented ?ugge+ng ;zg ;a:",:

tional diaqnostlc approach combxnang the lnformstion obtai- ned from A) Clinical 8) Brain imaging and C) Cere-

diagnosis. Clinically, CSF examination lays a vital role in the diagnosis of man mours and cerebra i

"secondary B ementias". such as brain tu- infections (e.g. Borrelia encephalitis).

(VAD). the major differential diagnosis for AD. Thus, CSF-GM1 have a potential as a biochemical marker for new ronal and synaptic degeneration in AD. Potential "negative" biochemical markers may serve to exclude a cerebrovascular component in AD. Sulfatide is the major acidic gl cosphin- golIpid in myelin. We have shown an u~crease in C F-sulfa- % tide in VAD as compared with AD and controls. Thus CSF-sul- fatide have a potential as a biochemical marker for vhite- -matter lesions, i.e., to exclude mixed AD/VAD.

110 RHEOLOGICAL MEASUREMENTS OF WHOLE BLOOD FROM

ALZHEIMER’S DISEASE, DIALYSIS AND

MULTINFARCTUAL DEMENTIA PATIENTS . a,eP.F. Zatta,

bA.M. Tollardo, CM. Favarato, oG. Bazzato, op. Moracchiello,

b,eM.Nicolini.aCentroCNR,Emocianine,Metalloproteine,bCUGAS

Universita’ di Padova, CDipartimento di Biologia, oDivisione

di Nefrologia, Ospedale Civile di Mestre-Venezia,

oDipartimento di Scienze Farmaceutiche, Italy. Blood is

considered as a non-Newtonian liquid with viscosity highly dependent on the

shear rates encountered in the vascular system. The experimental shear rate

range was assessed with the limit of Dmfn=l-s to Dmax = 200 -s. Subjecting

blood samples to increases in linear shear rate, the resulting values of shear

stress can be measured and the apparent viscositv calculated (n). Following

the recommendation of the International Commettee for Standardization in

Hematology the following formula was used: q 2oo( mPa s)=([t) 200 N -

rj 2oo P]/[T) 200 P]) x 100, defining the percent deviation of patient’s

blood data from those of healthy normal. Viscoelasticity of blood derives

mainly from aggregationldisaggregation of RBC’s and from the elastic

deformation of RBCs. In our study we considered the parameter: yisM)Blaslic

w(8). This parameter shows how the elastic and viscous components

of blood influence each other, when blood is subjected to an oscillating shear.

Blood viscosity(n) and viscoeleasticity as viscoelastic phase angle parameter

(6) have been investigated in 10 hemodialysis (before and after dialysis

treatment), 20 diagnosed Alzheimer’s and 24 multinfarctual cases with

respect to 10 healthy controls. Preliminary results showed a marked decrease

of n and S in pre-dialysis subjects, moderated decrease in multinfarctual and

AD patients with respect to the controls. Data will be presented in relation to

various hematic parameters.

111 INCREASED BETA2-MICROGLOBULIN @2-M) AND INTERLEUKIN-6 (IL6) IN SERUM PROM OLDER PERSONS WITH DOWN SYNDROME (DS). P.D.MEHTA, A.J.DALTON, S.P.MEHTA, M.PERCY AND H.M.WISNIEWSKI. Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA and Surrey Place Center, University of Toronto, Toronto, Ontario, Canada.

Persons with DS (40 years and older), who have come to autopsy show brain lesions similar to those seen in patients with Alzheimer disease (AD). It has also been noted that persons with DS have abnormal humoral and cell-mediated immune responses. Several recent studies have reported increased levels of acute phase proteins and cytokines in AD patients suggesting their role in the pathogenesis of AD. In order to test the hypothesis that increased levels of /l2-M (a marker for immune activation) and IL-6 (one of the cytokines with immunoregulatory effects) may also be found in serum from DS persons, we measured their levels in 41 DS persons (median age 56; range 31-68 years) and 41 normal controls (55; 29-68 years) by enzyme linked immunosorbent assay. Levels of b2-M were higher in DS sera (median 3.35; range 2.85-4.0 &ml) than in controls (2.15; 1.7-2.48) (p<.OOOl). IL-6 levels also were higher in DS sera (0.64, O-14 n&ml) than in contrclls (0; O-7.4) (pc.006). In addition, the above levels were compared in persons with DS who showed signs of memory failure associated with early stage of dementia of Alaheimer type (DAT) (n=lO, mean age 56) and those without evidence of such memory failure (n=lS, mean age 48). The values of p2-M between the two groups of DS were similar. However, the data showed significantly greater levels of IL-6 in DS persons with signs of DAT compared to those without signs of DAT (pc.05). We conclude that elevated levels of IL-6 may have resulted from an AD associated inflammatory reaction in older DS persons.

112 SERUM ANTI-HISTONES AND ANTI-dsDNA AUTOANTIBODIES IN ALZHEIMER’S DISEASE AND VASCULAR DEMENTIA. P. Mecocci, ??R. Ekman, L. Parnetti, D. Cadini, A. Longo, R. Cecchetti, E. FOB. A. Cherubini, U. Senin. Inst. Gerontology and Geriatrics, University of Perugia, 06100 Perugia, Italy, * Dept. Psychiatry and Neurochemistry, University of Lund, 22009, Lund, Sweden. Many reports suggested the involvement of the immune system in several neuropsychiatric pathologies and antibodies against nuclear components have been revealed in patients with chronic mental disorders. In this study we investigated presence of autoantibodies against histones and ds-DNA in sera of 110 subjects, using specific ELISA tests. Patients were divided in four groups: controls (no 23) vascular dementia (VD) (no 31) presenile Alzheimer’s disease (AD) (no 9) and senile Alzheimer’s disease (SDAT) (no 47). Degree of dementia was rated by means of MMSE and GBS scale which evaluates motor, intellectual and emotional disturbances. Serum anti-histones antibodies titer was significantly higher in SDAT compared to controls and VD (pdO.05). Also VD had anti-hi&ones titer higher than controls (p<O.O5). These results were not influenced by age, sex or duration of illness. Correlation analysis between anti- histones titer (expressed as OD in ELISA test) and neuropsychological scores showed a significant correlation when all demented patient were evaluated together: MMSE (r = -0.37, p<O.OOl). GBSm (r = 0.30, p<O.Oi), GBSi (r = 0.47, p<O.Wl), GBSe (r = 0.32, p<O.Ol). Within each clinical group VD subjects showed a significant relationship between anti-histones titer and, respectively, MMSE (r=-0.39, peO.05) and GBSi (r = 0.39, peO.05). AD showed the highest correlation between anti-histones serum titer and, respectively, MMSE (r = -0.69. pcO.O5), GBSm (r = 0.91, p<O.OOl), GBS-i (r = 0.92, p<O.OOl), GBSe (r = 0.76, p<O.Ol) scores. On the other hand no relationship was found in SDAT. Anti-dsDNA autoantibodies were found in high titer only in 1AD and PSDAT. On the basis of these results anti-histones autoantibodies seem related to disturbances of immunological functions in demented patients. lnfact their levels are extremely low in age matched controls. Probably this is a secondary defect but the extremely high correlation between autoantibodies titer and degree of dementia in AD could also suggest the involvement of immunological mechanisms in the pathogenesis of this specific type of dementia.