JOAN SMITH SONNEBORN, PHD.
PROFESSOR EMERITUS
UNIVERSITY OF WYOMING
ZOOLOGY & PHYSIOLOGY

VIDEO
OBJECTIVES 1
VISUALIZATION OF ALZHEIMER’S
DISEASE BRAIN; UNDERSTANDING
ALZHEIMER’S DISEASE
Objective 2
ADVANCES IN BRAIN VISUALIZATION IN
LIVING PATIENTS
Objective 3
EXERCISE DELAYING MEMORY LOSS
USING AN ALZHEIMER MOUSE MODEL

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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

 HUMAN DRUG TRIAL UPDATES
 WHAT SUPPLEMENTS & LIFESTYLES
WORK
 TECHNOLOGIES: NEW DRUGS; NEW BAD
GENES

*Gandy et al.AUG 2010.

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TOXIC PARTICLES
OLIGOMERS; FREE RADICALS.

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DECREASE IN PROTECTIVE CELL
ENVIRONMENT
INCREASE IN DAMAGE
ENVIRONMENT

.
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AGE DEPENDENT DECREASE IN:
1) PROTECTIVE PROTEINS
2) NERVE COMMUNICATION AGENTS
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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

 BOTH HAVE INSULIN RESISTANCE
 SHOW DECLINE IN KEY ENERGY PATHWAY
 USE SAME SPLICER TO CUT AMYLOID &
INSULIN
 CONTROL DIABETES; LOSE 5 POUNDS

 FLURIZAN, VACCINE TO
INDUCE IMMUNITY
 BAPINEUZUMAB, (PREFORMED
ANTIBODY IMMUNE AGENT)
 PBT2 COPPER TRANSFER

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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)
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

 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

 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

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

 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.
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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
.

*
VITAMIN 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.

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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

 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

•
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 PRECURSOR TO
ACETYLCHOLINE
 Foods with inositol, and uridine
 Lecithin membrane precursor eggs
.

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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 mouseonset of memory loss delayed*

*REDUCED MEMORY DEFICITS IN
ALZHEIMER MICE -STRONG
ANTIOXIDANT
Acetyl L carnitine : mitochondrial and energy generator, utilizes fatty acid, neuroprotective, memory enhancer; in AD studies

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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

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)**

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 lungsused 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.

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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.
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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

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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.

 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

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TELOMERES CAPS ON CHROMOSOMES
SHORTER CAPS ≈ SHORTER LIFE SPAN
 REPLACE CAPS, REPAIR &REJUVENATE
AGE DAMAGED NEURONS
 ACTIVATION OF ADULT CELL
REGENERATIVE CAPACITY

 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.

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ROLE OF TELOMERES
 ADULT STEM CELLS
 HORMESIS

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ENGINEERED AND “KNOCK-OUT” AND
INDUCIBLE KNOCK IN” MOUSE
 RESULT: ACCELLERATION OF AGING
REVERSED IN ALL ORGANS BY
INDUCING REPLACEMENT OF
TELOMERES.

 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.

 DELAY METABOLIC AGE VULNERABILITY
 ENHANCE PROTECTION STRATEGIES
AGAINST CULPRITS THAT STEAL
PRECIOUS MEMORIES.
 REDUCE CONCENRATION ON PLAQUES
AND TANGLES
 EXPLORE REGENERATIVE STRATEGIES

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

W yoming G eriatric E ducation C enter
307-766-2829
Please visit our website at: http://www.uwyo.edu/geriatrics/
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