NEURODEGENERATION, Vol. 4, pp 291-297 (1995) Distribution of Beta Amyloid Associated Proteins in Plaques in Alzheimer's Disease and in the Non-demented Elderly Shan-Shan Zhan, 1 Robert Veerhuis, 1,2 Wouter Kamphorst 2 and Piet Eikelenboom 1 Graduate School of Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Depts of Psychiatrf and Neuropathology 2 of the Medical Faculty, Amsterdam Recent studies have shown that cerebral beta amyloid (A[5)protein deposition is a necessary, but not sufficient, factor to develop the pathology of Alzheimer's disease (AD). In the present immunohistochemical study, we have investigated in AD the distribution of AI5 associated pro- teins in the cerebral neocortex, in the cerebellar cortex where A~ plaques are mainly of the diffuse type, and also in the cerebral neocortex of non-demented patients with A[5plaques. Results show that immunolabeling for Clq, C4c, C3d, 0~I-ACT and Apolipoprotein E (ApoE) occurs in the great majority of A~ plaques in all groups. ApoJ is present in A~ plaques of the cerebral neocortex in AD and in non-demented elderly, but is almost absent from those of the AD cerebellar cortex. C4Bp and P-component, in contrast to AD, rarely occurs in A[5 plaques of the cerebral neocortex in the non-demented elderly. Heparan sulphate proteoglycan (HSPG) core protein and inter- cellular adhesion molecule-1 (ICAM-1) are absent in the diffuse A[5 plaques in the AD cerebellum. These differences in distribution and expression of A~ associated proteins may be determined by brain region specific factors (cerebral cortex versus cerebellar cortex) and clinical state (demented versus non-demented cases). We suggest that, besides A~ peptide, certain A[5 associated proteins are required for both amyloid plaque formation and for the induction of neurofibrillary changes. © 1995 Academicpress Limited Key words: Alzheimer's disease, A[5 associated proteins THE AMYLOID PLAQUEis one of the pathological hall- marks of Alzheimer's disease (AD). Beta amyloid pro- tein (AIS), a 39- to 43-amino-acid peptide derived from a precursor membrane glycoprotein (amyloid precur- sor protein, APP), is the principal protein component. Recently, it has become apparent that a number of other proteins are associated with A[5 deposits---so called 'pathological chaperones'--but which are not themselves components of the A[5 fibrils. It has been suggested that some of these proteins are involved in a balancing between maintaining the solubility of A~ peptide (Ghiso et al., 1993) and its deposition, and/or Correspondence to: P. Eikelenboom, Dept of Psychiatry, PCA Valeriuskliniek, Valeriusplein 9,1075 BG Amsterdam, The Netherlands Received 9 March 1995; revised and acceptedfor publication 3 May 1995 © 1995 Academic Press Limited 1055-8330/95/030291 +7 $12.00/0 amyloid fibril formation (Snow et a l., 1994a). However, their precise functions and roles in the brain in AD are still unclear. A[3 amyloid plaques can be principally divided into two types: neuritic or senile plaques containing amy- loid filaments and dystrophic neurites with glial reac- tion; and diffuse or amorphous plaques without neuritic and glial changes (Rozemuller et al., 1989a). A[~ deposits in the cerebellum in AD consist mainly of diffuse plaques and they do not usually progress to form amyloid fibrils, neuritic alterations and glial changes (Joachim et al., 1989). Recently, we and others (Arai et al., 1990; Cras et al., 1991; Schmidt et al., 1991; Yasuhara et al., 1994; Zhan et al., 1995) have shown that the altered neurites of neuritic plaques in the cerebral cortex differ in AD from those in the non-demented elderly, since these can be immunostained by anti- bodies to tau, in contrast to those in the non-demented elderly which cannot. These data imply that although 291