Robin M Voigt-Zuwala

Rush University Medical Center

2 Parkinson’s Action Network, National Center for Health Statistics

Motor Symptoms

Resting Tremor

Rigidity

Bradykinesia/Akinesia

Postural Instability

Non-Motor Symptoms

Depression

Apathy

Fatigue

Dementia

3

Dopamine Hypothesis

4 Olanow et al, Neurology Neurology: 72, 2009

Years-Decades before PD

Olfactory Deficits

Chronic Constipation

5

Qin et al, Fundamental Clin Pharmacol, 2008

Liu et al, Neurotoxicology, 2008

PD-like

symptoms

LPS

Forsyth et al, PLoS One: 6(12), 2011

HC PD

Α-Syn

2y pre diagnosis

6

Microbiota

Barrier Integrity

Inflammation

Increased Pro-Inflammatory Bacteria Akkermansia

Oscillospira

Bacteroides

Decreased Anti-Inflammatory Bacteria Blautia

Copprococcus

Roseburia

PICRUSt Analysis Increased Type III secretion proteins

7

Keshavarzian et al, Mov Disorders: 30(10), 2015

Blautia

p=0.03*

HC Feces

(n=31)

PD Feces

(n=34)

0

10

20

30

40

50

% A

bu

nd

an

ce

Coprococcus

p=0.03*

HC Feces

(n=31)

PD Feces

(n=34)

0

5

10

15

8

Forsyth et al, PLoS One: 6(12), 2011

PD

HC

E. Coli Sugar Test

Administer: Sucralose,

Sucrose, Lactulose, Mannitol

Measure: Urinary sugar

content

9 Forsyth et al, PLoS One: 6(12), 2011

Increased mRNA:

Tlr4, Irak2, Tollip, Il1b, Il17a,

Ifng, Ifnb1, Il7r, Il8, Ccl5, Ccr5

HC

PD

3-NT

Α-Syn

2y pre-diagnosis

5y pre-diagnosis

HC

PD

PD

10

Microbiota

Barrier Integrity

Inflammation

Circadian

Rhythm

Disruption

Causes: Intestinal Dysbiosis,

Intestinal Leakiness,

Intestinal Inflammation

Videnovic et al, JAMA Neurol: 71(4), 2013

• Lower melatonin amplitude &

AUC (Videnovic et al 2014, Breen et al 2014)

• Altered Bmal1/2 & Per1 levels (Breen et al 2014, Gu et al 2015, Ding et al 2011, Cai

et al 2011)

• Altered rest/activity rhythms (Lees et al 1988, Tandberg et al 1998, Rye et al 2000,

Abbott et al 2005, Van Hilton et al 1991, 1993, 1994,

Bonuccelli et al 2000, Whitehead et al 2008)

• Altered body temp regulation (Suzuki et al 2007)

12

Future studies will be

necessary to fully

characterize circadian

rhythms in PD

Circadian

Disruption

Intestinal Dysbiosis,

Barrier Dysfunction, &

Inflammation

Parkinson’s

Disease

13

• Ali Keshavarzian

• Kathleen Shannon

• Christopher Forsyth

• Hemraj Dodiya

• Phillip Engen

• Maliha Shaikh

Mr. & Mrs. Larry Field