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Correspondence |

Parkinson Disease: Extranigral, Multisystem, and α-Synuclein “Plus”

Michail E. Kalaitzakis, PhD; Manuel B. Graeber, MD, PhD, FRCPath; Stephen M. Gentleman, PhD; Ronald K. B. Pearce, MD, PhD, FRCPC, FRCP
Arch Neurol. 2009;66(7):910-916. doi:10.1001/archneurol.2009.140.
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The review by Lim et al1 reminds its audience that Parkinson disease (PD) is a multisystem disorder. While the review addresses the multiplicity of derangements in the PD brain with resultant clinical manifestations and also alludes to pathologic findings other than α-synuclein deposition, certain further facts need to be mentioned in the context of “extranigral” pathologic findings.

Lim and colleagues state that “the Braak staging scheme . . . has been largely confirmed by other investigators . . . ”1 and thereby cite an article by Dickson et al.2 In fact, the study by Dickson and colleagues did not seek explicitly to address the staging of α-synuclein deposition. Rather, it demonstrated that in incidental Lewy body disease cases, α-synuclein pathologic findings were observed simultaneously in multiple regions of both the central and peripheral nervous systems, implying “a multicentric process from its earliest stages” and thus contradicting a predictable caudorostral progression of α-synuclein pathologic findings. While failing to support the Braak hypothetical staging of α-synuclein pathologic findings, the incidental Lewy body disease cases identified by Dickson and colleagues also had a mean Braak PD stage of 3; it was therefore unsurprising that there was robust correlation with markers of neuronal loss and dysfunction as compared with control subjects and patients with PD.

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