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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
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American Health Assistance Foundation
www.ahaf.org
Research and educational programs covering:Alzheimers DiseaseMacular Degeneration
Glaucoma
Visit us at www.ahaf.org1 (800) 437 2423
Swanson and Bota, PNAS 2010
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American Health Assistance Foundation
www.ahaf.org
Research and educational programs covering:Alzheimers DiseaseMacular Degeneration
Glaucoma
Visit us at www.ahaf.org1 (800) 437 2423
http://www.cccmkc.edu.hk/~kei-kph
http://www.ahaf.org/http://www.give.org/seal.asp?ID=3305112007http://www.ahaf.org/7/31/2019 Advances in Basic Research
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Visit us at www.ahaf.org1 (800) 437 2423
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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
Visit us at www.ahaf.org1 (800) 437 2423
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General topic outline
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.
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
Visit us at www.ahaf.org1 (800) 437 2423
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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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Role of Basic Science
Visit us at www.ahaf.org1 (800) 437 2423
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Visit us at www.ahaf.org1 (800) 437 2423
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,
genetics, clinical trials)
1. Role of Basic Research
2. The Basics of Basic Research in AD:
What is a plaque and tangle
oligomers?
3. Hot topics
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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What are the plaques and tangles?
http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg
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What are the plaques and tangles?
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)
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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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What are the plaques and tangles?
http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg
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General topic outline1. Recent advances in, and the role of, basic research
(avoiding causes and prevention, genetics, ADNI,
genetics, clinical trials)
1. Role of Basic Research2. The Basics of Basic Research in AD:
3. Hot topics
Amyloid Aggregation
Tau Spreading
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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Amyloid Aggregation
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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)
Visit us at www.ahaf.org1 (800) 437 2423
l l
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General topic outline1. Recent advances in, and the role of, basic research
(avoiding causes and prevention, genetics, ADNI,
genetics, clinical trials)
1. Role of Basic Research2. The Basics of Basic Research in AD:
3. Hot topics
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
Visit us at www.ahaf.org1 (800) 437 2423
http://www.give.org/seal.asp?ID=33051120077/31/2019 Advances in Basic Research
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CSF measurements
Visit us at www.ahaf.org1 (800) 437 2423
CS
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CSF measurements
Visit us at www.ahaf.org1 (800) 437 2423
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
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Bl d AB
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Blood ABeta measurements(Less invasive, more uncertain)
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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?)
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G l t i tli
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General topic outline1. Recent advances in, and the role of, basic research
(avoiding causes and prevention, genetics, ADNI,
genetics, clinical trials)
1. Role of Basic Research2. The Basics of Basic Research in AD:
3. Hot topics
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
Visit us at www.ahaf.org1 (800) 437 2423
P li i l D D l t d Di
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Preclinical Drug Development and Discovery
Visit us at www.ahaf.org1 (800) 437 2423
P li i l D D l t d Di
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Preclinical Drug Development and Discovery
Visit us at www.ahaf.org1 (800) 437 2423
P li i l D D l t d Di
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Preclinical Drug Development and Discovery
Visit us at www.ahaf.org1 (800) 437 2423
P li i l D D l t d Di
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Preclinical Drug Development and Discoveryrepurposing old drugs: bexarotene preclinical studies
Visit us at www.ahaf.org1 (800) 437 2423
http://www.dementiatoday.com/?p=20584
Preclinical Dr g De elopment and Disco er
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Preclinical Drug Development and Discovery
Visit us at www.ahaf.org1 (800) 437 2423
General topic outline
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General topic outline1. Recent advances in, and the role of, basic research
(avoiding causes and prevention, genetics, ADNI,
genetics, clinical trials)
1. Role of Basic Research2. The Basics of Basic Research in AD:
3. Hot topics
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
Visit us at www.ahaf.org1 (800) 437 2423
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
http://www.give.org/seal.asp?ID=3305112007