Serum α1-antichymotrypsin is not a useful marker for Alzheimer\'s disease or dementia in Parkinson\'s disease

J Neural Transm [P-D Sect] (1993) 6:145-149

Journal o f Neural Transmission 9 Springer-Verlag 1993 Printed in Austria

S e r u m a l - a n t i c h y m o t r y p s i n is not a useful marker for Alzheimer's disease or dementia in Parkinson's disease M. A. Kuiper 1, G. J. van Kamp 1, P. L. M. Bergmans 2, Ph. Scheltens 1, and E. Ch. Wolters I Departments of 1Neurology, and 2Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands Accepted May 10, 1993

Summary. We measured serum al-antichymotrypsin (ACT) levels in patients with Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy (MSA) and age-matched controls to evaluate whether serum ACT levels in AD patients were elevated and whether ACT levels in PD patients with dementia differed from those in PD or AD. None of the patient groups displayed an increase in ACT levels. We conclude that serum ACT is not useful as a marker, nor in AD nor in dementia in PD. Keywords: al-Antichymotrypsin, neurodegeneration, Alzheimer's disease, Parkinson's disease, dementia, multiple system atrophy. Introduction The serine protease inhibitor al-antichymotrypsin (ACT) is a serum glycoprotein with a molecular mass of 68kDa, and is synthesized in the liver and the brain. ACT, an acute phase reactant, can be elevated due to different causes, such as inflammation, trauma, surgery or tumor. Both in Alzheimer's disease (AD) and in Parkinson's disease (PD) signs of active inflammation have been found (McGeer et al., 1988). Moreover, ACT has been identified as one of the components of senile plaques in brains of AD patients (Abraham et al., 1988). There are several hypotheses considering the origin of ACT in senile plaques. Plaques could be the result of chronic inflammation, and ACT (with other acute phase proteins) is hypothesized to participate in plaque formation (Giometto et al., 1988). However, ACT deposits may as well be considered the result of plaque formation, as ACT is said to have a trophic effect on neurons (Kanai et al., 1991). ACT was found to be elevated in serum and cerebrospinal fluid (CSF) of AD patients (Matsubara et al., 1990; Brugge et al., 1992) and therefore serum ACT has been proposed as a screening marker for AD (Matsubara et al., 1990). There are, however, also studies in which these results could

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not be c o n f i r m e d ( F u r b y et al., 1991; D e l a m a r c h e et al., 1991) and conseq u e n t l y d o u b t has b e e n cast o n the usefulness of A C T as a biological m a r k e r for A D . In P D , not only an active i n f l a m m a t o r y process in the substantia nigra (pars c o m p a c t a ) has b e e n r e p o r t e d ( M c G e e r et al., 1988) but also A l z h e i m e r - l i k e p a t h o l o g y (Daniel and Lees, 1991). T h e latter m a y be a m a j o r factor in causing d e m e n t i a in PD. S e r u m A C T levels of P D patients w e r e r e p o r t e d as being n o r m a l by M a t s u b a r a et al. (1988). W e m e a s u r e d s e r u m A C T - l e v e l s in A D and P D patients, d e m e n t e d ( P D D ) and n o n - d e m e n t e d , as well as in patients with multiple system a t r o p h y ( M S A ) , to investigate (1) w h e t h e r s e r u m A C T levels in p a t i e n t groups differed f r o m controls, and (2) w h e t h e r s e r u m A C T levels in A D and P D D patients differed f r o m A C T levels in P D a n d M S A patients and (3) w h e t h e r s e r u m A C T levels in A D patients differed f r o m A C T levels in PDD. Patients and methods

Patients We measured serum ACT concentrations in 63 PD patients, 15 PDD patients, 10 AD patients, 12 MSA patients and 21 age-matched controls. PD patients included in this study were diagnosed as clinically idiopathic PD: they displayed at least two of the three main features of PD (tremor, rigidity and bradykinesia), lacked atypical features (pyramidal or cerebellar signs, autonomic failure or vertical gaze palsy) and responded favourably to dopaminergic medication. The diagnosis of dementia in PD was made according to the DSM-III-R criteria and confirmed by neuropsychological assessment. In patients, who had been clinically diagnosed as MSA (Quinn, 1989), this diagnosis was confirmed by IBZM-SPECT scan with the finding of a reduced binding potential of the dopamine D2 receptor in the striatum (Schwarz et al., 1992). The diagnosis of "probable" AD was made according to the NINCDS-ADRDA criteria (McKhann et al., 1984). Patients or controls with recent infection, tumor, paraproteinemia, recent surgery or traumata, were excluded. All patients were recruited from our out-patient's clinic, while age-matched controls were the healthy spouses of the patients. Method ACT concentration was measured in serum by single radial immunodiffusion (RID) in a buffered agarose gel, using rabbit anti-human-ACT antibodies (A 022, DAKO A/S, Glostrup Denmark). A standard line with an ACT concentration ranging from 10.3 to 165 mg/L was constructed, diluting Protein Standard Plasma (human) OTFI 07 supplied by Behringwerke (Marburg, Germany). Serum samples were diluted 8-fold; all dilutions were made with phosphate-buffered saline. A calibration curve was constructed from the square of the diameter of the precipitation rings and the ACT standards of known concentrations. These paramaters showed a correlation of r = 1.00. CV was better than 1 percent. Serum ACT levels are expressed in mg/L. Statistics Mann-Whitney's rank sum test was used to compare groups. P-values