1. A Correlation Between Alzheimer’s and Parkinson’s: Inflammatory Response to Endogenous Neuro-protective Mechanisms Peter H. Massey

2. “Brain Attacks” α CVDs are the principal cause of death in Western civilizations, accounting for more than 40% of all deaths. α Cerebrovascular Disease – disease of blood vessels supplying the brain - Sustained hypertension - narrow, stiff, deformed α Stroke – loss of blood supply – leads to paralysis α Aneurysm – blood filled dilation of blood vessel – if ruptured extremely harmful α Ischemia – temporary paralysis http://medicalimages.allrefer.com/large/stroke.jpg

3. Protein Activation α Basal ganglia - dopamine & acetylcholine - transmission of nerve impulses http://stemcells.nih.gov/StaticResources/info/scireport/images/figure82.jpg http://www.nature.com/nrn/journal/v2/n7/images/nrn0701_492a_f2.gif

4. Parkinson’s Basics http://www.mitosciences.com/images/parkinsons.jpg http://www.about-dementia.com/articles/images/ParkinsonsDopamine.jpg α Parkinson's disease - between the ages of 50 and 65 - 1% of the population

5. Symptoms Parkinson’s α Slowness of voluntary movements, especially in the initiation of such movements as walking or rolling over in bed α Decreased facial expression, monotonous speech, and decreased eye blinking α A shuffling gait with poor arm swing and stooped posture α Unsteady balance; difficulty rising from a sitting position α Continuous "pill-rolling" motion of the thumb and forefinger α Abnormal tone or stiffness in the trunk and extremities α Swallowing problems in later stages Alzheimer’s α Dementia: both long term and short term in later stages of life α Loss of reasoning & logic

6. Parkinson’s Linked to Alzheimer’s α Alpha-synuclein - accumulate into Lewy bodies inside nerve cells - found in the amyloid plaques in Alzheimer's disease α Alpha-synuclein - binds to membranes on nerve cells – lipids (Deniz, March 2009 - PNAS) http://len.epfl.ch/webdav/site/len/shared/import/migration/parki1_1.jpg

7. Inflammatory Response α Inflammation - response to infection or injury - Damaged tissue releases chemicals - attract white blood cells - Cytokines - accelerate inflammation http://lpi.oregonstate.edu/ss03/lipoicacid.html

8. Inflammatory Response (continued) α Inflammatory cytokines - stimulate production of adhesion molecules - adhesion molecules prone to atherosclerosis - important target for treatment of atherosclerosis & CVD α Inflammatory molecules - recruitment of white blood cells into the blood vessel wall - abnormal foam cells & atherosclerotic lesions α Alpha-lipoic acid - ‘metal chelators’- inhibit white blood cell recruitment - preventing infection and inflammation - reducing oxidative stress - bolstering antioxidant defenses http://www.nature.com/nrn/journal/v7/n1/images/nrn1829-f3.jpg

9. Inflammation Linked to Parkinson’s α Nurr1 - transcription factor α Nurr1 protein - microglia & astrocytes - Microglia are macrophage-like cells - immune defense in the central nervous system - Astrocytes - large star-shaped support functions (keep cell alive) α Absense of Nurr1 - inflammation increased - toxic effect on those neurons University of California - San Diego (2009, April 6). Protein Protects Neurons In Brain From Damage Due To Inflammation. ScienceDaily.

10. Observing Brain Activity α Brain Culture – advantageous – one specimen over prolonged period α Fluorescence microscopy α Induced axonal damage α Inflammatory response initiated α Axonal regeneration observed http://www.neuro-zone.com/writable/content_attachments/neurons%20in%20network.jpg http://www.amicusvisualsolutions.com/obrasky/06015_02W.jpg

11. Treatment α Balance of the neurotransmitters acetylcholine & dopamine α Success with experiments involving operative procedures - too invasive http://www.herbsandtinctures.co.uk/images/maca-capsules.jpg

12. α-Lipoic Acid α Anti-inflammatory: cell signaling processes; sensitivity, metabolism, and stress response α Inflammation & cell cycle control α Reproduces endogenous anti-oxidants: glutathione, vitamin C and E α Removes superoxide anions, hydroxyl radicals, and other toxic ROS from body (the cell) α Both hippocamal regions and basal ganglia (hydrophilic & hydrophobic) α Related to inflammation & oxidative stress http://aging-management.com/images/Lipoic-acid-2D-skeletal.png

13. Sepsis Hotchkiss and Nicholson Nature Reviews Immunology advance online publication; published online 13 October 2006 | doi:10.1038/nri1943

14. Sepsis-associated Encephalopathy α Feinstein Institute for Medical Research Dr. Sangeeta Chavan - sepsis Dr. Kevin Tracey – Vagus nerve stimulation block inflammatory response leading to disease (sepsis) α Encephalopathy – infection of blood – brain dysfunction (may be due to direct infection of spinal cord) - Sepsis – whole body inflammatory state http://focosi.altervista.org/sepsis.jpg

15. Selected References