Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes.
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.
Neuropathology Unit, Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, Charing Cross Campus, St Dunstan's Road, London, UK. michail.kalaitzakis03@imperial.ac.uk
M E
ME
Kalaitzakis
A J
AJ
Walls
R K B
RK
Pearce
S M
SM
Gentleman
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D003704:Dementia / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
D016229:Amyloid beta-Peptides; D015415:Biomarkers