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et al. (Cell Tissue Res, 318, 121, 2004) have suggested that <strong>the</strong>se synuclein-positive neurites <strong>an</strong>d<br />

inclusions first appear in <strong>the</strong> medulla be<strong>for</strong>e adv<strong>an</strong>cing to <strong>the</strong> pons, midbrain <strong>an</strong>d cerebral cortex.<br />

We have previously reported that RNF11, <strong>an</strong> E3 ubiquitin ligase, localizes to Lewy bodies in PD<br />

brains. To develop a comprehensive underst<strong>an</strong>ding of RNF11-associated neuropathology in PD<br />

patients we per<strong>for</strong>med a comparative <strong>an</strong>alysis of <strong>the</strong> distribution of α-synuclein <strong>an</strong>d RNF11<br />

pathology in brain regions associated with <strong>the</strong> progression of PD. Age-matched control, PD, <strong>an</strong>d<br />

PD/AD (PD with Alzheimer's Disease pathology) brain tissues were obtained <strong>from</strong> Emory’s<br />

brain b<strong>an</strong>k. Adjacent 50-µm thick free-floating sections through <strong>the</strong> brain stem (BSt) regions,<br />

subst<strong>an</strong>tia nigra (SN) <strong>an</strong>d cingulate cortex (Ctx) were processed <strong>for</strong> α-synuclein or RNF11<br />

immunohistochemistry. α-synuclein pathology was revealed using a p<strong>an</strong>-α-synuclein <strong>an</strong>tibody<br />

<strong>an</strong>d <strong>an</strong> <strong>an</strong>tibody specific to oxidized <strong>for</strong>ms of α-synuclein. RNF11 was immunolabeled using <strong>an</strong><br />

<strong>an</strong>tibody against <strong>the</strong> full-length protein. Immunolabeled sections were scored semiqu<strong>an</strong>titatively<br />

<strong>from</strong> 0 to 5, with 5 representing <strong>the</strong> most severe pathology. No α-synuclein- or RNF11-positive<br />

inclusions were detected in control cases used in this study. Extensive (scores=4-5) α-synucleinpositive<br />

Lewy bodies <strong>an</strong>d Lewy neurites were detected in BSt followed by moderate (scores=3-<br />

4) pathology in SN <strong>an</strong>d mild (scores=1-2) pathology in Ctx, in most (7 of 11) but not all PD <strong>an</strong>d<br />

PD/AD cases. Three cases had more extensive α-synuclein pathology in <strong>the</strong> SN <strong>an</strong>d Ctx th<strong>an</strong> in<br />

BSt; one case had mild (1) pathology in all <strong>the</strong> regions examined. The distribution of RNF11<br />

pathology paralleled that of α-synuclein pathology in all 11 cases. However, <strong>the</strong> degree of<br />

RNF11 pathology was less in 5 cases, greater in two cases, <strong>an</strong>d similar in four cases to αsynuclein<br />

pathology. Our data indicate that RNF11-positive neuropathology follows a pattern of<br />

regional distribution similar to PD-related α-synuclein pathology, streng<strong>the</strong>ning <strong>the</strong> association<br />

of RNF11 with PD.<br />

Disclosures: R. Betarbet, None; D.N. Karmali, None; D.S. Cooper, None; M. Gearing,<br />

None; J.J. Lah, None; A.I. Levey, None; A.L. Orr, None.<br />

Poster<br />

530. Parkinson's Disease: Hum<strong>an</strong> Related<br />

Location: South Hall A<br />

Time: Tuesday, October 20, <strong>2009</strong>, 8:00 am - 12:00 noon<br />

Program#/Poster#: 530.22/J32<br />

Topic: C.03.b. Hum<strong>an</strong> studies<br />

Support: NIH/NIEHS ES015777<br />

Title: Genetic m<strong>an</strong>ipulations of RNF11 <strong>an</strong>d α-synuclein aggregation

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