ILADS National Meeting Philadelphia, Pennsylvania Borrelia and Alzheimer’s Disease
Alan B MacDonald, MD St. Catherine of Siena Medical Center, Smithtown, New York
PDF created with pdfFactory Pro trial version www.pdffactory.comImages in this presentation are reproduced from COPYRIGHT MATERIALS
with full details of original copyright available upon request from the presenter
Alan B. MacDonald, MD PDF created with pdfFactory Pro trial version www.pdffactory.com
Alzheimer’s
patterns of
injury Nerve cell loss
PDF created with pdfFactory Pro trial version www.pdffactory.com How do we know? PDF created with pdfFactory Pro trial version www.pdffactory.com
Is the Textbook version correct?
PDF created with pdfFactory Pro trial version www.pdffactory.com
Should We Kill the Messenger?
• “Lyme Borreliosis”
• Vs
• “Lyme Disease”
• Allowed Manifestations
• Arthritis, Carditis, Skin- “it is”,Meinigitis
PDF created with pdfFactory Pro trial version www.pdffactory.com
Ducks and Hunters
a
Tale of Three
Medical Specialists
PDF created with pdfFactory Pro trial version www.pdffactory.com
Flies like a duck
• Checklist
Do I Know what a Duck looks
like?
You are allowed to shoot ducks
in hunting Season
You are not allowed to Shoot other birds
in duck hunting season
PDF created with pdfFactory Pro trial version www.pdffactory.com
• Walks like a Duck
• Quacks like a duck
• Hunting Season …..ISSUES
PDF created with pdfFactory Pro trial version www.pdffactory.com
**
*
*
The Story
• Enter …Stage left
•
Pathologist
•
•
Radiologist
“Super” Medical specialist****
( Casting note: )
the “Super” medical specialist must
be bigger than life, and
Never Never Never in Doubt ..
………about
or …….his/her Good looks…
personal infallibility
PDF created with pdfFactory Pro trial version www.pdffactory.com
Sure, Swift and Wrong
Director to Alan :
“Tell the joke NOW!!!”
Do not Tell the Punch line yet!!!!
PDF created with pdfFactory Pro trial version www.pdffactory.com
Dog swims back to the
Duck blind
• What does a Duck look like??
PDF created with pdfFactory Pro trial version www.pdffactory.com
Acts 1,2,3
•
Is it a Duck ??
•
IT HAS TO BE a Duck !!!
•
What
did I DO WRONG ???
PDF created with pdfFactory Pro trial version www.pdffactory.com
Ducks for Dummies
PDF created with pdfFactory Pro trial version www.pdffactory.com
The sum of its parts
Can You Identify the duck if you only see
A Keyhole view …
Can you “Connect the Dots???”
PDF created with pdfFactory Pro trial version www.pdffactory.com
Connecting…..
The Dots …. Figurative and Literal
PDF created with pdfFactory Pro trial version www.pdffactory.com In DementiaYou loose the Ability to ….
Connect the dots PDF created with pdfFactory Pro trial version www.pdffactory.com Dementia in Syphilis • Noguchi • Nonne • A Morality Play • Science versus Dogma • 500 years of Medical “Intelligence” vs• A Contrary View from the Loyal Opposition
PDF created with pdfFactory Pro trial version www.pdffactory.com Mise en Scene • Central Islip, Long Island, New York • Mentally Ill persons in a Warehouse • Locked Up • Left to Die • Forgotten • Ignored PDF created with pdfFactory Pro trial version www.pdffactory.com
A National Hero
from Japan
• Enter Stage Left
• Hideyo Noguchi, MD
PDF created with pdfFactory Pro trial version www.pdffactory.com
Act One
• Syphilis 30 years ago
• Dementia, develops slowly
• Personality changes
• Lost to Society
PDF created with pdfFactory Pro trial version www.pdffactory.com
Skip to …Act Three
• Autopsy study of the Brain
• 70 cases
• 58 negative for Treponema Pallidum
• 12 Positive for the Spiral Bacterium
• A New paradigm proposed
• Old paradigm Overturned
PDF created with pdfFactory Pro trial version www.pdffactory.com
Act Two
• Clinical thinking about Syphilitic
Dementia
• “Coincidence” versus “Causation”
• Persistence of an infection for 30 years • Clinical thinking
• Pathology based thinking • A Grrreat Experiment will offer answers PDF created with pdfFactory Pro trial version www.pdffactory.com Helen Marioni • Syphilis in her past • Dementia • Hospitalization – “Long Term Parking” • Antibiotic treatment • Clinical Improvement • Dementia is REVERSED PDF created with pdfFactory Pro trial version www.pdffactory.com
Helen’s handwriting after
Penicillin
PDF created with pdfFactory Pro trial version www.pdffactory.com
TEXTBOOK
MEDICINE
“ TEXTBOOK EXAMPLES”
THE “Central Dogma” –
…………. And
Dogma – “Rewritten and Corrected Version”
?Should I Apologize for
Treating Dementia with Antibiotics?
Look it up!!!
PDF created with pdfFactory Pro trial version www.pdffactory.com
Images of Truth
Rewritten
• Thank you
• Dr Barry Marshall and Dr. Robin Warren
Nice Wallpaper Barry and Robin What’s the Pattern????? PDF created with pdfFactory Pro trial version www.pdffactory.comThe Medical – Industrial Complex Apologies
• “Dr. Marshall and Dr. Warren, please accept our apologies
for unkind words and for uncollegial thoughts …. You were Right 20 years ago …. The textbooks Got it wrong>>>>> PDF created with pdfFactory Pro trial version www.pdffactory.com Take HOME MESSAGE • A microbe • Recovered • From a diseased • Tissue • May be the CAUSE • OF THE DISEASE PDF created with pdfFactory Pro trial version www.pdffactory.com “NORMAL FLORA” • Is there • A • “normal” flora • In the • CENTRAL NERVOUS SYSTEM??? • …..please vote on this question PDF created with pdfFactory Pro trial version www.pdffactory.com Borrelia burgdorferi is not normal flora PDF created with pdfFactory Pro trial version www.pdffactory.comPhilosphical Issues on Microbiology Idiopathic Diseases.
Are Fair Game For microbiologists and Molecular Pathologists PDF created with pdfFactory Pro trial version www.pdffactory.com Let us go Hunting PDF created with pdfFactory Pro trial version www.pdffactory.com
Plaques
GVB
Tangles
Alzheimer’s Disease –
Microscopic paradigms
PDF created with pdfFactory Pro trial version www.pdffactory.com
?
Treponema
pallidum
model
for
dementia
PDF created with pdfFactory Pro trial version www.pdffactory.com
+
+
+
Positive
results
in plaque in culture spirochetes in brain
PDF created with pdfFactory Pro trial version www.pdffactory.com
?
Treponema
pallidum
model
for
dementia
PDF created with pdfFactory Pro trial version www.pdffactory.com
+
+
+
+
Positive results
in plaque
in culture spirochetes DNA in
Plaque PDF created with pdfFactory Pro trial version www.pdffactory.com
Positive
results independent replicated … and
?? So what PDF created with pdfFactory Pro trial version www.pdffactory.com2005 Miklossy beta Amyloid changes by Borrelia burgdorferi
PDF created with pdfFactory Pro trial version www.pdffactory.com
2005 MacDonald GVB
are positive for Borrelia burgdorferi DNA
PDF created with pdfFactory Pro trial version www.pdffactory.com
Take this GVB,… Please
PDF created with pdfFactory Pro trial version www.pdffactory.com
GVB deciphered
• Cytoplasm, … Not in the Nucleus
• Rounded “granules”
• Vacuole “surround”
• Size differences in granules
• Variable number of granules
PDF created with pdfFactory Pro trial version www.pdffactory.com
GVB “Checklist”
Alzheimer’s disease
Hippocampus
Variable in Number
Granules vary in size ---little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
In Situ Dna and Rat Tissue culture
PDF created with pdfFactory Pro trial version www.pdffactory.com
GVB
PROFILES
Binder Lab
Northwestern
Univ. School
of Medicine
PDF created with pdfFactory Pro trial version www.pdffactory.com
MIKLOSSY RAT TISSUE
CULTURE
PDF created with pdfFactory Pro trial version www.pdffactory.com
MacDonald
human Alzheimer In situ DNA
PDF created with pdfFactory Pro trial version www.pdffactory.com
Human Alzheimer
In situ DNA hybridization for
Borrelia burgdorferi DNA
Granules vary in size – from little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
Miklossy
Rat nerve cell
H5332 monoclonal +
Granules vary in size – from little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
Human nerve cell not diseased from Alzheimer Brain
AO stain Acridine Orange DNA = Yellow to green RNA = red to orange PDF created with pdfFactory Pro trial version www.pdffactory.com 2004
Miklossy
Rat Neuron Tissue Culture with B. burgdorferi
PDF created with pdfFactory Pro trial version www.pdffactory.com
Human Nerve cell from Alzmeimer Brain with + cytoplasmic DNA
What is Cylindrical, contains DNA and is capable of invading the Cytoplasm??
PDF created with pdfFactory Pro trial version www.pdffactory.com
Miklossy rat
nerve cell
in tissue culture with B. burgdof. Spirochete inside the cell
What is cylindrical, contains DNA and is capable of invading the cytoplasm??
PDF created with pdfFactory Pro trial version www.pdffactory.com
Miklossy rat nerve cell tissue culture with B.burgdorf spirochete inside the cell
PDF created with pdfFactory Pro trial version www.pdffactory.com
Human Nerve cell from
Alzheimer’s with GVB
and ? Spirochetal form at 9 oclock
Granules vary in size – from little to big
What is cylindrical, contains DNA and is capable of invading the cytoplasm ??
PDF created with pdfFactory Pro trial version www.pdffactory.com
Miklossy 2005 Rat nerve cells
PDF created with pdfFactory Pro trial version www.pdffactory.com
2004
Miklossy
Rat Neuron Tissue Culture with B. burgdorferi OSP A + “dots”
Granules vary in size from little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
GVB Alzheimer hippocampus
PDF created with pdfFactory Pro trial version www.pdffactory.com
Borrelia burgd. In transformation
to granular forms
Granules vary in size – from little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
Alzheimer brain
H5332 – OSP A-
outer surface protein B.Burgdorf
Granules vary in size – from little to big
PDF created with pdfFactory Pro trial version www.pdffactory.com
DNA= yellow/green
RNA= red
Granular zones of DNA =Yellow/green and RNA = red
PDF created with pdfFactory Pro trial version www.pdffactory.com
Cyst forms emerging
from Borrelia burgdorferi
DNA inside Cysts / Rounded forms
is yellow,
RNA inside Cysts = Red
PDF created with pdfFactory Pro trial version www.pdffactory.com
Striated (striped) DNA/Rna
patterns in Borrelia burgdorferi
PDF created with pdfFactory Pro trial version www.pdffactory.com
Cystic forms outnumber all others acridine orange stain for DNA / Rna
DNA in Spirochetal Cysts = Yellow/green RNA in spirochetal Cysts = Red PDF created with pdfFactory Pro trial version www.pdffactory.com
Segments- some with DNA
some with Rna
PDF created with pdfFactory Pro trial version www.pdffactory.com
Tangles – the loose ends
PDF created with pdfFactory Pro trial version www.pdffactory.com
Tangles + Tau staining
PDF created with pdfFactory Pro trial version www.pdffactory.com
Tangles – diseased microtubules?
PDF created with pdfFactory Pro trial version www.pdffactory.com
Broken or Ruptured Spirochetal Cyst forms and
Plaques of Alzheimer’s A Structural link PDF created with pdfFactory Pro trial version www.pdffactory.com
Plaques in Alzheimer’s
PDF created with pdfFactory Pro trial version www.pdffactory.com
Plaque
Density
a measure of Alzheimer severity
PDF created with pdfFactory Pro trial version www.pdffactory.com
One Alzheimer Plaque with Amyloid center
PDF created with pdfFactory Pro trial version www.pdffactory.com
?Plaque
?central
core ?circular ring zone
PDF created with pdfFactory Pro trial version www.pdffactory.com
Comparison of Plaques
PDF created with pdfFactory Pro trial version www.pdffactory.com
Comparisons with Edgerton
Edgerton’s “splash” is a “Broken” Drop
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson – Dynamic equilibrium of Borrelia burgdorferi cysts to vegetative forms
Cysts as “droplets” - eligible to participate in a “splash” PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson Cysts Alone
A cyst is a “Water Balloon – like structure”
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson – “Stress Altered”
euphemism for Cyst form
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson – vegetative forms of
B.Burgdorferi
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson – Conversion to Cystic
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson Cystic
“stress
altered” form
PDF created with pdfFactory Pro trial version www.pdffactory.com
Nelson Cyst form with Blebs
PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson and Brorson
Cyst forms of B. burgdorferi
PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson
evolving Cyst forms of Bb
PDF created with pdfFactory Pro trial version www.pdffactory.com
MacDonald 1987 Cyst form H9724 + Alzheimer Brain
A “water balloon” containing Granules PDF created with pdfFactory Pro trial version www.pdffactory.com
..
MacDonald – Aged B31 Bb
H9724 +
Cyst form attached to Vegetative
Compare with Brorson Cysts
A water Balloon –like structure with
granules inside it
PDF created with pdfFactory Pro trial version www.pdffactory.com
MacDonald – 1987 Cyst form Alzheimer Brain H 9724+
A water balloon like structure with Cylinders or fibers inside it PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson cyst
forms
of
Borrelia
burgdorferi
Acridine Orange stain
DNA = Yellow /green
RNA = Red
PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson
Cyst of Borrelia burgdorferi with Granules
Borrelia burgdorferi B31 -Comparison PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson Cyst of B. Burgdorferi compared with MacDonald Cyst
from Alzheimer brain PDF created with pdfFactory Pro trial version www.pdffactory.com
Alzheimer
brain
Cysts H9724 positive with inner granular elements
PDF created with pdfFactory Pro trial version www.pdffactory.com
Brorson Cystic Bb
by Electron microscopy
PDF created with pdfFactory Pro trial version www.pdffactory.com
Hayes 1983
Bacteriophage of Bb
Inside / Outside of the membrane labeled by attached Bacteriophage
“Tail” of the
Phage is the
Hypodermic
needle
PDF created with pdfFactory Pro trial version www.pdffactory.com
Noguchi’s legacy
PDF created with pdfFactory Pro trial version www.pdffactory.com
Noguchi’s spirochetes
PDF created with pdfFactory Pro trial version www.pdffactory.com
Fikrig’s primate model
PDF created with pdfFactory Pro trial version www.pdffactory.com
Fikrig’s Fla B “Ruler”
Primate Brain DNA Probes
PDF created with pdfFactory Pro trial version www.pdffactory.com
Fikrig’s
Gene probes for DNA of Bb
PDF created with pdfFactory Pro trial version www.pdffactory.com
Molecular Interrogation
Early studies of Alzheimer’s
PDF created with pdfFactory Pro trial version www.pdffactory.com
8
Molecular Interrogation cases positive for Fla B Probe PCR
PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
Site of the PCR Product in Fla B
of Borrelia burgdorferi PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
Thanks
to
Turn the
Corner
Foundation
PDF created with pdfFactory Pro trial version www.pdffactory.com
PDF created with pdfFactory Pro trial version www.pdffactory.com
Support
for this
scientific investigation
from
Turn the Corner Foundation New York, New York and ILADS
is gratefully acknowledged PDF created with pdfFactory Pro trial version www.pdffactory.com