Transcript alzheimer research advances

ALZHEIMER RESEARCH
ADVANCES
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
TOPICS






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 (CONTD.)



HUMAN DRUG TRIAL UPDATES
WHAT SUPPLEMENTS & LIFESTYLES
WORK
TECHNOLOGIES: NEW DRUGS; NEW BAD
GENES
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
WHY IN ELDERLY?


.
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
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 omega3 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 & FOLATEe
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.
*
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 mouseonset 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 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.
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.
Wyoming Geriatric Education Center
307-766-2829
Please visit our website at:
http://www.uwyo.edu/geriatrics/
______________________________