ALZHEIMER RESEARCH ADVANCES

JOAN SMITH SONNEBORN, PHD.

PROFESSOR EMERITUS

UNIVERSITY OF WYOMING

ZOOLOGY & PHYSIOLOGY

VIDEO OBJECTIVES 1VISUALIZATION OF ALZHEIMER’S DISEASE

BRAIN; UNDERSTANDING ALZHEIMER’S DISEASE

Objective 2ADVANCES IN BRAIN VISUALIZATION IN

LIVING PATIENTSObjective 3EXERCISE DELAYING MEMORY LOSS

USING AN ALZHEIMER MOUSE MODEL

MUST REMOVE STIGMA OF ALZ DISEASE PRODROMAL Alzheimer’s-Earliest Stage. WHERE MICE & NUNS STUDIES MEET REAL CULPRITS STEALING MEMORY?

TOXIC AMYLOID; FREE RADICALS HEY! WHY ARE THE ELDERLY TARGETED DIABETES AND ALZHEIMER RELATIONS

TOPICS

HUMAN DRUG TRIAL UPDATES WHAT SUPPLEMENTS & LIFESTYLES

WORK TECHNOLOGIES: NEW DRUGS; NEW BAD

GENES

TOPICS (CONTD.)

WHERE NUN AND MICE STUDIES MEET

Plaques & tangles FOUND in nuns & mice not showing memory loss!!

In mice*, memory loss without plaques & tangles.

*Gandy et al.AUG 2010.

CULPRITS IN ALZHEIMER’S DISEASE

TOXIC PARTICLES OLIGOMERS; FREE RADICALS.

HEY! WHY IN ELDERLY?

DECREASE IN PROTECTIVE CELL ENVIRONMENT

INCREASE IN DAMAGE ENVIRONMENT

AGE DEPENDENT DECREASE IN: 1) PROTECTIVE PROTEINS

2) NERVE COMMUNICATION AGENTS

AGE DEPENDENT INCREASE IN: 1) TOXIC FRAGMENTS

2) NOX (noxious) ENZYME PRODUCTION. 3) EXPRESSION OF FAMILY OF DAMAGE GENES.

4) GLUTAMATE EXCESS 5) COPPER EXCESS

6)” AGING GENE” EXPRESSION

.

WHY IN ELDERLY?

DIABETES-ALZHEIMER’S:SHARED PROBLEMS:

BOTH HAVE INSULIN RESISTANCE SHOW DECLINE IN KEY ENERGY PATHWAY USE SAME SPLICER TO CUT AMYLOID &

INSULIN CONTROL DIABETES; LOSE 5 POUNDS

HUMAN DRUG TRIALS

FLURIZAN, VACCINE TO INDUCE IMMUNITY

BAPINEUZUMAB, (PREFORMED ANTIBODY IMMUNE AGENT)

PBT2 COPPER TRANSFER

VACCINE FLURIZAN TARGETED A (AMYLOID BETA) (HBO) INVESTED $200BILLION & 8 YEARS IN

FLURIZAN DID SHOW REDUCTION IN PLAQUES &

TANGLES BUT HEALTH COMPLICATIONS & NOT SIGNIFICANT EFFECT ON MEMORY LOSS. STUDY DISCONTINUED

RECENT HUMAN TRIALS (CONTINUED)

BAP; PBT2 USES PREMADE ANTIBODY (BAP),

SUCCESS IN SUBPOPULATION NOT CARRYING SUSCEPTIBILITY GENE APO-E-4 **

Phase 3 trial still in progress.

PBT2 phase 2 : COPPER TRANSPORTER

RESTORES ALZ NEURON PROJECTIONS* & COMMUNICATION PROTEINS LOST IN DISEASE IN MICE

Reduces amyloid, improves function on Neuropsychological test Battery

(NTB) in 12 weeks IN HUMANS

*(humanized monoclonal antibody TO AMYLOID)- **1/3 OF ALZ NOT CARRIERS; E 4 INTERFERS WITH TAU STICKING TO MICROTUBLES and susceptibility to oxidation;

Dendritic spine density and synaptic protein levels in a mouse model

Reduces amyloid, improves function on Neuropsychological test Battery NTB in 12 weeks

ENVIRONMENT &ALZHEIMER’S ENVIRONMENTAL ENRICHMENT

REDUCES AMYLOID IN MICE MODEL

RESTORES MEMORY IN MOUSE MODEL

NOVELTY , CHANGE IN MENU, CARD GAMES, SCENERY CHANGE, VISITING GROUPS, DANCE INSTRUCTORS, CHILDREN VERSION BINGO GAMES FOR DEMENTIA PATIENTS, ANIMAL VISITS

.

STRESS REDUCTION

MUSIC

Ipods with personalized music to soothe or invigorate individual.

SUPPLEMENTS, MINERALS AND FOODS:

Omega 3, Uridine: Like anti -anxiety Drugs Prozac and SSRI

Inositol: Like Valium

EXERCISE

SUPPLEMENTS?

INOSITOL, OMEGA-3 FATTY ACIDS, URIDINE, CURCUMIN, ANTIOXIDANTS, VITAMIN D, C, E, FOLATE, LIPOIC ACID, RESVERATROL

ANTI DEPRESSION SUPPLEMENTS, SUPPLEMENTS: URIDINE AND OMEGA-3 TOGETHER

MATCHED WITH EFFECTS OF PROZAC AND SSRI’S DRUGS IN MICE*

URIDINE stimulate synthesis of CHOLINE, OMG increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine.

URIDINE FOODS: Organ meats (liver, pancreas),Tomatoes, Brewer’s yeast , Beer, **Broccoli

Omega 3 (polyunsaturated fats) foods:cold water fish, such as salmon, or flaxseeds, walnuts, winter squash

* . Omega 6 Omega-6s contribute to inflammation in the body, while omega-3 modulates

• **Carlezon et al., 2005 Biol Psychiatry 57 (4): 343–50. • ***Yamamoto et al., Metab Clin Exp 51 (10): 1317–23.

ANTI ALZHEIMER SUPPLEMENT VITAMIN D & FOLATEeVITAMIN D : ↑ Transports out cell garbage ,↑ Regulates nerve

health pathways; No D intensifies deficit in spatial learning in ALZ patients.**

FOLATE

Required : brain health, function and development

↓ blood pressure and arterial stiffness

Supplement in 60 year olds reduced ALZ risk after 10 years.

Advanced Alzheimer’s Disease lowest folate levels.

Deficiency in institutions & nursing homes: people with absorption problems such as ulcerative colitis and people taking certain medications e.g., methotrexate.

dark green leafy vegetables oranges, lentils, beans, asparagus, broccoli, cauliflower, liver and brewer's yeast.

*

CELL MEMBRANE AND INSULATION

Saturated fats and cholesterol are significant portion of insulation (myelin sheath) around nerve fibers.

Born with 100% phosphatidylcholine (lecithin); only have 10% in elderly major constituent of all cell membranes including nerve cells

Major Source of lecithin egg yolks

SUPPLEMENTS

INOSITOL,and choline is lecithin- ingredient in cell membrane, signal processes, increase acetylcholine and serotonin.↑ positive mood ↓ copper excess, ↑ hair growth.

Treats schizophrenia and hypoglycemia. Mimics Valium.

Also acetylcysteine: glutamate receptor

ANTI-ALZ SUPPLEMENTS

OMEGA-3 FATTY acids ↓ amyloid & tau protein, EPA low in suicide patients, DHA OMG-3s

URIDINE (CHOLINE PRECURSOR): ↑ acetylcholine, repairs synapse membrane in neurons , membrane, damage= dementia

Omega 3 and Uridine supplements are antidepressant, like PROZAC and SSRI in bipolar disorder, reduces amyloid

CURCUMIN (Tumeric,curry, seasoning)*, antioxidant, promotes healthy gene expression.

•

CHOLINE and membrane FOODS CHOLINE PRECURSOR TO

ACETYLCHOLINE Foods with inositol, and uridine Lecithin membrane precursor eggs

.

SIRTUINS: RESVERATROL

Anti Aging supplement. “ Molecule modifier”s required for participation/ initiation in major metabolic processes (Deacetylases)

Activates “Notch” gene pathway for protection against stress, nerve damage ,and inhibition of enzyme that generates amyloid.

Crossed AD mouse with high sirtuin mouse-onset of memory loss delayed*

LIPOIC ACID* & ACETYL CARNITINE*REDUCED MEMORY DEFICITS IN

ALZHEIMER MICE -STRONG ANTIOXIDANT

Acetyl L carnitine : mitochondrial and energy generator, utilizes fatty acid, neuroprotective, memory enhancer; in AD studies

SUNDOWNER* SNACK?

BANANA, PAPYA, DATES (without skin),, ORANGES**, MELON** increase serotonin, and acetylcholine.

No wheat or rye

Promotes serotonin (GOOD MOOD) AND breakdown to melatonin (sleep enhancer) –circadian rhythm hormone and “jet lag intervention”

*describes the onset of confusion and agitation that generally affects people with dementia or cognitive impairment and usually strikes around sunset.

** inositol source neuronal membrane and neurotransmitters

CHOCOLATE AND HEALTH

23.6 million people will die from cardiovascular disorders.

High chocolate consumption (5x/week) associated with 30% risk reduction in: heart diseases, stroke, ie., lowered blood pressure, cholesterol, atherosclerosis, and insulin resistance. Increased brain blood flow in elderly.*Dramatic effect at least in part due to triggering release on Nitric oxide (NO)**

Chocolate & Theobromide

Milk chocolates 20-50% less theobromide (caffeine like chemical) than dark.

Action::diuretic, stimulant, blood pressure relaxer, allows blood flow, relax bronchi muscles in the lungs- used in cough medicine.

Acts on the vagus nerve, which runs from the lungs to the brain.

Poison for dogs and horses and humans that metabolize theobromine slowly, including some elderly.

EXERCISE IN ELDERLY

Falls: leading cause of injury, death and disability among persons 65 years and older

By 2020, falls in over 65 about $43.8 billion/yr. Weight training: increases bone density and

bone facture risks. Bone loss 5% per decade after 40. Age associated muscle loss reversible

Number of falls from frail women 80 reduced by half in a year with weight training. Some over 90, used cane instead of walker, could get out of chair, and increased mobility.

"ACSM's Health & Fitness Journal"; Benefits of Physical Activity in Older Adults; Angela Fern; Sept/Oct 2009, * Fiatarone Tufts University in Boston

Exercise in Elderly IN NURSING HOME (cont) Reduces prescriptions, doctor visits, emergency

calls, orthopedic devices cost, and extent of care needed.

Increases mobility and decreases deficits in ADLs; can feed themselves, get out of chair.

Improves cognition, mood, and self image. Improves muscle mass, joints, and strength for

balance Provides intervention in diabetes, osteoporosis,

depression, and obesity and required associated care requirements.

EXERCISES

CHAIR STAND, STANDING LEG CURL, SIDE HIP RAISE, BICEP CURL, OVERHEAD PRESS, UPWARD ROW, TOE STAND** ANKLE & WRIST WEIGHTS

LESS FAT,MORE MUSCLE, BONE LOSS PREVENTED OR REVERSES LOSS, INCREASES, STRENGTH, ENERGY , BALANCE, AND FLEXIBILITY.

*Miriam Nelson, Ph.D. 2 “Strong Women Stay Young” 2 sessions/week ISBN 0-553-38077-X

TELOMERES, ADULT STEM CELLS, & REPROGRAMS

TELOMERES CAPS ON CHROMOSOMES SHORTER CAPS ≈SHORTER LIFE SPAN REPLACE CAPS, REPAIR &REJUVENATE

AGE DAMAGED NEURONS ACTIVATION OF ADULT CELL

REGENERATIVE CAPACITY

REGENERATIVE MEDICINE

TAP INTO HORMETIC RESPONSE (a little bit of bad is good, a lot is bad)

Major protective pathways are inducible by stress for repair and regeneration that respond to immediate threat, but repair age damage as well even in the very old.

Response can be triggered by known small molecule triggers.

ALTERNATIVE METHODLOGY AGING INTERVENTIONS ROLE OF TELOMERES ADULT STEM CELLS HORMESIS

TELOMERE REPLACEMENT REVERSES AGING ENGINEERED AND “KNOCK-OUT” AND

INDUCIBLE KNOCK IN” MOUSE RESULT: ACCELLERATION OF AGING

REVERSED IN ALL ORGANS BY INDUCING REPLACEMENT OF TELOMERES.

ADULT STEM CELLS

STEM CELLS THROUGHOUT ADULT CAPABLE OF REJUVENATION WITH

MASTER SWITCHES SIGNALS BEST SOURCES: UMBILICAL CORD,

AMNIOTIC FLUID, WISDOM TEETH, AND GUM TISSUE.

DURING DEVELOPMENT DIFFERENTIATION TO CELL TYPE; NOT UNIDIRECTIONAL-CAN REVERSE.

CONCLUSION

DELAY METABOLIC AGE VULNERABILITY ENHANCE PROTECTION STRATEGIES

AGAINST CULPRITS THAT STEAL PRECIOUS MEMORIES.

REDUCE CONCENRATION ON PLAQUES AND TANGLES

EXPLORE REGENERATIVE STRATEGIES

CONCLUSION: HOPE

THERE IS REAL PROMISE OF DELAY OF ONSET AND PROGRESSION OF ALZHEIMER’S DISEASE IN OUR IMMEDIATE FUTURE.

307-766-2829

Please visit our website at:http://www.uwyo.edu/geriatrics/

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Wyoming Geriatric Education Center