Transcript Applications of Nanotechnology in Alzheimer`s Disease

Applications of Nanotechnology in
Alzheimer’s Disease
BioE 494 – Atomic and Molecular Nanotechnology
Fall 2007
Deivya Bansal
Outline
What is Alzheimer’s disease?
 What is some of the current research being
done?
 How does nanotechnology play a role?
 What are some future directions that can be
taken using nanotechnology?

WHAT IS ALZHEIMER'S
DISEASE?
Alzheimer’s Disease

Neurodegenerative disease

Most common form of dementia ~60% worldwide
Memory, cognition, thought and language
are primary impact areas
 Costs over $100 billion a year
 Final confirmation occurs via post-mortem
inspection


Presence of plaques and tangles
Alzheimer’s Disease

Plaques

Incorrectly folded amyloid-β proteins
 Recall

the 4 structures of protein folding
Neurofibrillary tangles
Hyperphosphorylation of tau protein
 Makes it aggregate
 Found within neurons of those with AD

 Not
completely understood
Alzheimer’s Disease
This shows images of normal brain tissue
versus brain tissue afflicted with
Alzheimer’s disease.1
1Mattson,
Mark. “Pathways Towards and Away from
Alzheimer’s Disease.” Nature 430 (2004): 631-639.
This image shows positron emission
tomography (PET) of a normal brain versus
one with Alzheimer’s disease. 1
Diagnosis of Alzheimer’s
disease
3Sunderland,
Trey; Hampel, Harald; Takeda, Masatoshi; et.al. “Biomarkers in the Diagnosis of
Alzheimer’s Disease: Are We Ready?” Journal of Geriatric Psychiatry and Neurology 13 (2006):
172-179.
WHAT IS SOME OF THE
CURRENT RESEARCH BEING
DONE?
Current Research

Understand etiology of disease
Includes specimen examination
 EEG examination


Detecting and testing biomarkers in
cerebrospinal fluid and in plasma


Show biochemical impact on neurons
Development of new drugs aimed to keeping
biochemical balance within brain
Current Research

Lumbar puncture
being performed


~150 mL of fluid is
in direct contact
with brain

2Andreasan,
Niel and Blennow,Kaj. “CSF
biomarkers for mild cognitive impairment and
early Alzheimer’s disease.” Clinical Neurology
and Neurosurgery 107 (2005): 165-173.
Access to
cerebrospinal fluid
See biochemical
makeup of fluid
HOW DOES
NANOTECHNOLOGY PLAY A
ROLE?
Use of Nanotechnology
 Detection
 Drug
of biomarkers
Delivery
Nanotechnology and Biomarker
Detection
Nanotechnology and Biomarker
Detection

Bio-Barcode Assay
Ultrasensitive
 Can detect any concentration making it ideal for
AD diagnosis
 Uses oligonucleotide-modified nanoparticles


Localized Surface Plasmon Resonance
(LSPR) Nanosensor

Sensitive to changes in refractive index near
surfaces of gold and silver nanoparticles
Bio-Barcode Assay
3Keating,
Christine D. “Nanoscience
enables ultrasensitive detection of
Alzheimer’s biomarker.” Proceedings
of the National Academy of Sciences
102 (2005): 2263-2264.
4Georganopoulou, Dimitra G., et al.
“Nanoparticle-based detection in
cerebral spinal fluid of a soluble
pathogenic biomarker for Alzheimer’s
disease.” Proceedings of the National
Academy of Sciences 102 (2005):
2273-2276.
Nanotechnology and Drug
Delivery

Nanoparticle encapsulated

Thioflavin-T
 Antioxidant

Chelation Therapy

Iron Chelate
4Liu,
Gang et al. “Nanoparticle
Iron Chelators: A new therapeutic
approach in Alzheimer disease
and other neurologic disorders
associated with trace metal
imbalance.” Neuroscience Letters
406 (2006): 189-193.
5 Hartig, Wolfgang, et.al.
“Electron microscopic analysis of
nanoparticles delivering thioflavinT after intrahippocampal injection
in mouse: implications for
targeting β-amyloid in Alzheimer’s
disease.” Neuroscience Letters
338 (2003): 174-176.
Nanoparticle Encapsulation

Targeted drug delivery

Testing done for:
 Vitamin
E
 Thioflavin-T

Nanoparticles similar to LDL
Identifies with LDL receptors
 Easier passage through blood brain barrier

Chelation Therapy

Chelator – Compound that binds to free
metal ions

Iron chelator most commonly used for AD
 Preferred
chelator is desferrioxamine (DFO)
 Other metals associated with AD: aluminum and zinc

Conjugated with nanoparticles
 Easier
transport across blood brain barrier
WHAT ARE SOME FUTURE
DIRECTIONS THAT CAN BE
TAKEN USING
NANOTECHNOLOGY?
Thank you!
Questions?
References







Mattson, Mark. “Pathways Towards and Away from Alzheimer’s Disease.” Nature 430 (2004): 631-639.
Andreasan, Niel and Blennow,Kaj. “CSF biomarkers for mild cognitive impairment and early Alzheimer’s
disease.” Clinical Neurology and Neurosurgery 107 (2005): 165-173.
Sunderland, Trey; Hampel, Harald; Takeda, Masatoshi; et.al. “Biomarkers in the Diagnosis of Alzheimer’s
Disease: Are We Ready?” Journal of Geriatric Psychiatry and Neurology 13 (2006): 172-179.
Liu, Gang et al. “Nanoparticle Iron Chelators: A new therapeutic approach in Alzheimer disease and other
neurologic disorders associated with trace metal imbalance.” Neuroscience Letters 406 (2006): 189-193.
Hartig, Wolfgang, et.al. “Electron microscopic analysis of nanoparticles delivering thioflavin-T after
intrahippocampal injection in mouse: implications for targeting β-amyloid in Alzheimer’s disease.” Neuroscience
Letters 338 (2003): 174-176.
Georganopoulou, Dimitra G., et al. “Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic
biomarker for Alzheimer’s disease.” Proceedings of the National Academy of Sciences 102 (2005): 2273-2276.
Keating, Christine D. “Nanoscience enables ultrasensitive detection of Alzheimer’s biomarker.” Proceedings of the
National Academy of Sciences 102 (2005): 2263-2264.