Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other Parkinsonian syndromes M.E. Kalaitzakis ⁎, A.J. Walls, R.K.B. Pearce, S.M. Gentleman Neuropathology Unit, Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, Charing Cross Campus, St Dunstan's Road, London, UK, W6 8RP abstract article info Article history: Received 24 March 2010 Revised 29 September 2010 Accepted 7 October 2010 Available online 14 October 2010 Keywords: Parkinson's disease Dementia Striatum Amyloid-β peptide [ 11 C]PIB ligand Dementia with Lewy bodies Neuropathology Lewy body disease Recent neuropathological studies have described widespread amyloid-β peptide (Aβ) deposition in the striatum of patients with Lewy body disorders, particularly in Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). However, positron emission tomography (PET) studies using the [ 11 C]PIB ligand, binding to Aβ deposits, detects significant striatal pathology only in DLB and not in PDD. Employing immunohistochemistry, we examined striatal Aβ deposition in the caudate nucleus and putamen of 52 PD, 41 PDD, 14 DLB, 7 multiple system atrophy (MSA) and 14 progressive supranuclear palsy (PSP) cases in relation to the presence of dementia. PD, MSA and PSP cases showed little or no Aβ pathology in the striatum. In contrast, both PDD and DLB cases demonstrated significantly greater Aβ deposition in the striatum when compared to PD, MSA and PSP groups. We conclude that striatal Aβ pathology is common in both PDD and DLB and may reflect the development of dementia in these conditions. More detailed examination of the morphology of the Aβ pathology suggests that it is the presence of cored amyloid plaques in DLB, but not PDD, that underlies the differences seen in PET imaging. © 2010 Elsevier Inc. All rights reserved. Introduction Parkinson's disease (PD) is a neurodegenerative disorder charac- terized by the gradual onset and progression of both motor and non- motor disturbances (Fearnley and Lees, 1991). The defining patho- logical features of the disease are the loss of dopaminergic projection neurones of the substantia nigra pars compacta and locus coeruleus, as well as the presence of α-synuclein (αSyn) positive inclusions in cell bodies and cell processes of brainstem neurones, called Lewy bodies (LB) and Lewy neurites (LN), respectively. However, the pathology in PD exceeds the classical boundaries of the substantia nigra and locus coeruleus with involvement of multiple extranigral sites in both the central and peripheral (autonomic) nervous system (Braak and Braak, 2000). Co-morbid pathology characteristic of Alzheimer's disease (AD) is also often seen in patients with PD (Jellinger, 2009; Jellinger et al., 2002). Although PD is traditionally viewed as a movement disorder, non- motor complications, including dementia, are commonly seen in PD patients, with a prevalence of up to 50% (Emre, 2003; Emre et al., 2007). The risk for dementia in PD (PDD) increases with age and duration of disease (Emre, 2003) with other risk factors including age at onset, an akinetic-rigid syndrome, depression, early autonomic failure and a poor response to dopaminergic treatment (Aarsland et al., 1996; Emre et al., 2007; Hietanen and Teravainen, 1988; Reid et al., 1996). Despite a high incidence of dementia in PD (PDD) the precise anatomico-pathological basis for this remains unclear. Cortical, subcortical and limbic αSyn pathology have been linked to dementia in PD (Aarsland et al., 2005; Hurtig et al., 2000; Mattila et al., 2000), although other authors have described advanced αSyn pathology without clinical dementia (Parkkinen et al., 2005). We, and other groups, have demonstrated the presence of amyloid-β peptide (Aβ) pathology in the striatum of PDD and dementia with Lewy bodies (DLB) patients (Duda et al., 2002; Jellinger and Attems, 2006; Kalaitzakis et al., 2008; Liang et al., 2006). A possible distinction between PD, PDD and DLB on the basis of differences in Aβ striatal pathology has also been suggested (Jellinger and Attems, 2006; Kalaitzakis et al., 2008). Imaging studies, however, using Pittsburgh compound B ([ 11 C]PIB) positron emission tomography (PET), as a marker of brain amyloid deposition, have demonstrated an increased Aβ load in the striatum of DLB but not PDD patients (Edison et al., 2008). In this immunohistochemical study we set out to explore the significance of striatal pathology in Lewy body diseases by investi- gating the extent and nature of Aβ deposition in the striatum of PD (n = 52), PDD (n = 41), DLB (n = 14), multiple system atrophy (MSA) (n = 7) and progressive supranuclear palsy (PSP) (n = 14) cases in relation to the presence of dementia. Neurobiology of Disease 41 (2011) 377–384 ⁎ Corresponding author. E-mail address: michail.kalaitzakis03@imperial.ac.uk (M.E. Kalaitzakis). Available online on ScienceDirect (www.sciencedirect.com). 0969-9961/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.nbd.2010.10.005 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi