***

Oct 30, 2005

ILADS National Meeting Philadelphia, Pennsylvania Borrelia and Alzheimer’s Disease

Alan B MacDonald, MD   St. Catherine of Siena        Medical Center,   Smithtown, New York

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Images in this presentation are            reproduced from COPYRIGHT MATERIALS

    with full details of original copyright available upon request from the presenter

Alan B. MacDonald, MD

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  Alzheimer’s

patterns of

   injury Nerve cell loss

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  How do we know?

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  Is the Textbook version correct?

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  Should We Kill the Messenger?

• “Lyme Borreliosis”

• Vs

• “Lyme Disease”

• Allowed Manifestations

• Arthritis, Carditis, Skin- “it is”,Meinigitis

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  Ducks and Hunters

a

Tale of Three

Medical Specialists

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  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

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  • Walks like a Duck

• Quacks like a duck

• Hunting Season …..ISSUES

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  **

*

*

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

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  Sure, Swift and Wrong

Director to Alan :

“Tell the joke NOW!!!”

Do not Tell the Punch line yet!!!!

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  Dog swims back to the

Duck blind

• What does a Duck look like??

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  Acts 1,2,3

•

Is it a Duck ??

•

IT HAS TO BE  a Duck !!!

•

What

did I DO WRONG ???

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  Ducks for Dummies

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  The sum of its parts

Can You Identify the duck if you only see

A Keyhole view …

Can you “Connect the Dots???”

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  Connecting…..

The Dots ….   Figurative   and Literal

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  In Dementia

   You loose the Ability to ….

Connect the dots

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  Dementia in Syphilis

• Noguchi

• Nonne

• A Morality Play

• Science versus Dogma

• 500 years of Medical “Intelligence” vs

• A Contrary View from the Loyal Opposition

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  Mise en Scene

• Central Islip, Long Island, New York

• Mentally Ill persons in a Warehouse

• Locked Up

• Left to Die

• Forgotten

• Ignored

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  A National Hero

from Japan

• Enter Stage Left

• Hideyo Noguchi, MD

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  Act One

• Syphilis 30 years ago

• Dementia, develops slowly

• Personality changes

• Lost to Society

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  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

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  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

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  Helen Marioni

• Syphilis in her past

• Dementia

• Hospitalization – “Long Term Parking”

• Antibiotic treatment

• Clinical Improvement

• Dementia is REVERSED

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  Helen’s handwriting after

Penicillin

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  TEXTBOOK

MEDICINE

“ TEXTBOOK EXAMPLES”

THE “Central Dogma” –

…………. And

Dogma – “Rewritten and Corrected Version”

?Should I Apologize for

Treating Dementia with Antibiotics?

Look it up!!!

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  Images of Truth

Rewritten

• Thank you

• Dr Barry Marshall and Dr. Robin Warren

Nice Wallpaper

Barry and Robin

What’s the Pattern?????

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The 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>>>>>

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  Take HOME MESSAGE

• A microbe

• Recovered

• From a diseased

• Tissue

• May be the

CAUSE

• OF THE DISEASE

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  “NORMAL FLORA”

• Is there

• A

• “normal” flora

• In the

• CENTRAL NERVOUS SYSTEM???

• …..please vote on this question

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  Borrelia burgdorferi

is not normal flora

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  Philosphical Issues on Microbiology Idiopathic              Diseases.

Are Fair Game

For microbiologists

and Molecular Pathologists

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  Let us go Hunting

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  Plaques

GVB

Tangles

Alzheimer’s Disease –

Microscopic paradigms

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  ?

Treponema

pallidum

model

for

dementia

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  +

+

+

Positive

results

in plaque in culture spirochetes in brain

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  ?

Treponema

pallidum

model

for

dementia

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  +

+

+

+

Positive results

in plaque

in culture spirochetes DNA in

Plaque

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  Positive

    results independent replicated … and

?? So what

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   2005 Miklossy beta Amyloid changes by Borrelia burgdorferi

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     2005 MacDonald GVB

are positive for Borrelia burgdorferi      DNA

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  Take this GVB,… Please

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  GVB deciphered

• Cytoplasm, … Not in the Nucleus

• Rounded “granules”

• Vacuole “surround”

• Size differences in granules

• Variable number of granules

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  GVB “Checklist”

Alzheimer’s disease

Hippocampus

Variable in Number

Granules vary in size ---little to big

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In Situ Dna and Rat Tissue                 culture

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  GVB

PROFILES

Binder Lab

Northwestern

Univ. School

of Medicine

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  MIKLOSSY RAT TISSUE

CULTURE

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  MacDonald

human Alzheimer In situ DNA

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  Human Alzheimer

In situ DNA hybridization for

Borrelia burgdorferi DNA

Granules vary in size – from little to big

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  Miklossy

Rat nerve cell

H5332 monoclonal +

Granules vary in size – from little to big

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Human nerve cell not       diseased from     Alzheimer Brain

AO stain Acridine Orange

DNA = Yellow to green

RNA = red to orange

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  2004

Miklossy

      Rat Neuron Tissue Culture with B. burgdorferi

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   Human Nerve cell from Alzmeimer Brain with + cytoplasmic DNA

What is Cylindrical, contains DNA and is capable of invading the Cytoplasm??

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  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??

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  Miklossy rat nerve cell tissue    culture with     B.burgdorf     spirochete   inside the cell

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  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 ??

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  Miklossy 2005 Rat nerve cells

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  2004

Miklossy

  Rat Neuron Tissue Culture      with B.   burgdorferi     OSP A +       “dots”

Granules vary in size from little to big

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    GVB Alzheimer hippocampus

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  Borrelia burgd. In transformation

to granular forms

Granules vary in size – from little to big

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  Alzheimer brain

H5332 – OSP A-

outer surface protein B.Burgdorf

Granules vary in size – from little to big

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  DNA= yellow/green

RNA= red

Granular zones of DNA =Yellow/green and RNA = red

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  Cyst forms emerging

from Borrelia burgdorferi

DNA inside Cysts / Rounded forms

is yellow,

RNA inside Cysts = Red

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  Striated (striped) DNA/Rna

patterns in Borrelia burgdorferi

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Cystic forms outnumber      all others acridine orange stain for DNA /                 Rna

DNA in Spirochetal Cysts = Yellow/green

RNA in spirochetal Cysts = Red

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  Segments- some with DNA

some with Rna

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  Tangles – the loose ends

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  Tangles + Tau staining

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  Tangles – diseased microtubules?

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  Broken or Ruptured Spirochetal Cyst forms and

Plaques of Alzheimer’s

A Structural link

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  Plaques in Alzheimer’s

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  Plaque

Density

       a measure of Alzheimer severity

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     One Alzheimer Plaque with Amyloid center

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  ?Plaque

?central

   core ?circular ring zone

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  Comparison of Plaques

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  Comparisons with Edgerton

Edgerton’s “splash” is a “Broken” Drop

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Nelson – Dynamic equilibrium of Borrelia burgdorferi cysts to            vegetative forms

Cysts as “droplets” - eligible to participate in a “splash”

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  Nelson Cysts Alone

A cyst is a “Water Balloon – like structure”

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  Nelson – “Stress Altered”

euphemism for Cyst form

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  Nelson – vegetative forms of

B.Burgdorferi

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  Nelson – Conversion to Cystic

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  Nelson Cystic

“stress

altered” form

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  Nelson Cyst form with Blebs

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  Brorson and Brorson

Cyst forms of B. burgdorferi

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  Brorson

evolving Cyst forms of Bb

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MacDonald 1987 Cyst form H9724 + Alzheimer Brain

A “water balloon” containing Granules

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  ..

MacDonald – Aged B31 Bb

H9724 +

Cyst form attached to Vegetative

Compare with Brorson Cysts

A water Balloon –like structure with

granules inside it

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      MacDonald – 1987 Cyst form Alzheimer Brain H 9724+

A water balloon like structure with

Cylinders or fibers inside it

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  Brorson cyst

forms

of

Borrelia

burgdorferi

Acridine Orange stain

DNA = Yellow /green

RNA = Red

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  Brorson

Cyst of Borrelia burgdorferi with Granules

Borrelia burgdorferi B31 -Comparison

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Brorson Cyst of B. Burgdorferi compared with    MacDonald          Cyst

from

Alzheimer brain

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  Alzheimer

brain

Cysts H9724 positive with inner granular elements

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  Brorson Cystic Bb

by Electron microscopy

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  Hayes 1983

Bacteriophage of Bb

Inside / Outside of the membrane labeled by attached Bacteriophage

“Tail” of the

Phage is the

Hypodermic

needle

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  Noguchi’s legacy

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  Noguchi’s spirochetes

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  Fikrig’s primate model

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  Fikrig’s Fla B “Ruler”

Primate Brain DNA Probes

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  Fikrig’s

Gene probes for DNA of Bb

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  Molecular Interrogation

Early studies of Alzheimer’s

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  8

   Molecular Interrogation cases positive for Fla B Probe PCR

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Site of the     PCR Product in     Fla B

of Borrelia

burgdorferi

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  Thanks

to

Turn the

Corner

Foundation

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  Support

for this

scientific investigation

from

Turn the Corner Foundation New York, New York and                  ILADS

is gratefully

acknowledged

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