advances in basic research

7/31/2019 Advances in Basic Research

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Advances in Basic Research

Guy S. Eakin, Ph.D.Vice President Scientific AffairsAmerican Health Assistance Foundation

Visit us at www.ahaf.org1 (800) 437 2423
http://www.give.org/seal.asp?ID=3305112007


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American Health Assistance Foundation

www.ahaf.org

Research and educational programs covering:Alzheimers DiseaseMacular Degeneration

Glaucoma


Swanson and Bota, PNAS 2010
http://www.ahaf.org/http://www.give.org/seal.asp?ID=3305112007http://www.ahaf.org/


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American Health Assistance Foundation

www.ahaf.org

Research and educational programs covering:Alzheimers DiseaseMacular Degeneration

Glaucoma


http://www.cccmkc.edu.hk/~kei-kph
http://www.ahaf.org/http://www.give.org/seal.asp?ID=3305112007http://www.ahaf.org/


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General topic outline

1. Recent advances in, and the role of, basic research

(absent causes and prevention, genetics, ADNI, clinical

trials)

2. Non-neuroimaging approaches to early diagnosis

a. CSF and serum tests,

b. Neuro-psych approaches to diagnosis

3. Pre-clinical drug development and discovery

4. Traumatic brain injury



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1. Recent advances in, and the role of, basic research(avoiding causes and prevention, genetics, ADNI,

genetics, clinical trials)

1. Role of Basic Research

2. The Basics of Basic Research in AD

3. Hot Topics.








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Basic ClinicalTranslational

Research into fundamental

principles of science or

disease.

Research

designed to

transition basic

research to

clinical

interventions.

Determinations of safety

and efficacy of drugs for

human use

What refinements and costeffectiveness will predictacceptance by clinicians, insurers,etc?

What policy and best practicesresearch can assure maximal reachof any therapy?

Other

Translational

How does it work?What might be goingwrong?

Can it be manipulatedor fixed in humans?

How well does itwork?Is it safe?

Role of Basic ScienceCategories of research goals


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Role of Basic Science(vis vis the drug pipeline)



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Role of Basic Science



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General topic outline1. Recent advances in, and the role of, basic research

(avoiding causes and prevention, genetics, ADNI,


1. Role of Basic Research

2. The Basics of Basic Research in AD:

What is a plaque and tangle

oligomers?

3. Hot topics








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What are the plaques and tangles?

http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg


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LaFerla and Querfrurth, NEJM 2010


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Amyloid Plaques vs Oligomers(Is amyloid acting as a big bomb or as itty bitty bullets)


Researchers created oligomeronly

mice (no, or few plaques)

showed similar impairment to

standard models but without

presence of the plaques!

If a gene that restores plaques is

added back to the oligomer only mice:

no further impairment is noted.

Implications for plaque buster drugs


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http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg


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1. Role of Basic Research2. The Basics of Basic Research in AD:

3. Hot topics

Amyloid Aggregation

Tau Spreading








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Amyloid Aggregation


http://www.alz.org/research/diagnostic_criteria/preclinical_recommendations.pdf


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Amyloid Aggregation



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Tau Spreading(and the challenges of the word infectious)



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Tau Spreading(and the challenges of the word infectious)


l l


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3. Hot topics








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CSF measurements


CS


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CSF measurements


For Sporadic (Late onset) AD:

Clearance, but not production

of Abeta differs between AD

patients and controls

(Early onset and Downs

syndrome is a different story)

CSF


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CSF measurements


Bl d AB


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Blood ABeta measurements(Less invasive, more uncertain)


Meta analysis of 13 studies / >10,000 patients

AB42 levels or AB40 levels not predictive

Lower AB42:AB40 ratio had 1.67 risk ratio (increased risk)

"Despitethe limitations of existing researchandheterogeneity across thestudiesconsidered, this systematic review and meta-analysis suggeststhat the ratio ofplasma A42:A40 may have value in predicting the riskfor later development of dementia orAD and merits further investigation,"

I di id l Di i P l ti i k


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Individual Diagnosis or Populations risk(whats good for what?)


G l t i tli


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3. Hot topics







P li i l D D l t d Di


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Preclinical Drug Development and Discovery




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Preclinical Drug Development and Discoveryrepurposing old drugs: bexarotene preclinical studies


http://www.dementiatoday.com/?p=20584

Preclinical Dr g De elopment and Disco er


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3. Hot topics


a. CSF and serum tests,b. Neuro-psych approaches to diagnosis




Traumatic Brain Injury


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Traumatic Brain Injury

TBI patients show increased amyloid and tau deposition

Especially if the patient caries one or more APOE4 allele

And these APOE4 carriers are more susceptible (2 times as likely) to have

poor outcomes following TBI

Pig TBI was used to show that amyloid deposition followed TBI, rather than

preceded.



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Thank you.

Keep in touch!

Guy S. Eakin, [email protected] President Scientific AffairsAmerican Health Assistance Foundation

Visit us at www ahaf org

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