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Posted: Apr 11th, 2008
Nanotechnology solutions for Alzheimer's disease
(Nanowerk Spotlight) Alzheimer’s disease (AD), a brain disorder named for German physician Alois Alzheimer who first described it in 1906, is a disease that destroys brain cells, causing problems with memory, thinking and behavior. Alzheimer’s gets worse over time, and it is fatal. It is also the most common form of dementia. The latest estimate is that 26.6 million people were suffering from Alzheimer’s disease worldwide in 2006, and this number will rise to 100 million by 2050 - 1 in 85 of the total population. The latest 2008 data for the US alone estimates that 5 million Americans have the disease, with an estimated increase to 11 to 16 million by 2050. Not only does Alzheimer's have no cure, even its cause is unknown (research has led to several theories that are still being investigated). The onset of AD is usually very slow and gradual and, since there is no test for it, there is no clear-cut line between normal age-related changes and warning signs. An absolute diagnosis of AD can only be determined during the examination of brain tissue, which is usually done during an autopsy (if you want to find out more - the Alzheimer's Association has a lot of information on its website). A recent report provides an overview of the promises that nanotechnology brings in research on diagnosis and therapy of AD.
In the absence of a cure – since Alzheimer's is a progressive disease, and the brains natural regenerative capacity is thought to be minimal – an early diagnosis combined with some form of treatment that stops the pathogenic process is seen as the most promising way of battling the disease. However, as Dr. Amir Nazem and Dr. G. Ali Mansoori write in their paper (Nanotechnology Solutions for Alzheimer’s Disease: Advances in Research Tools, Diagnostic Methods and Therapeutic Agents), at the present there is not any single diagnostic tool for precise screening or early and accurate detection of the disease; and only a probable diagnosis with an 80% confidence, on average, is possible based on clinical criteria (including laboratory tests, neuroimaging and neuropsychological assessment).
Nazem, a scientists at the Qaem Hospital, Mashhad University of Medical Sciences in Iran and Mansoori a professor in the Departments of Bioengineering and Chemical Engineering & Physics at the University of Illinois at Chicago describe possible approaches to early diagnoses and effective treatment of AD. They write that the development of nanotechnology approaches for early-stage diagnosis of AD is quite promising but acknowledge that scientists are still at the very beginning of the ambitious project of designing effective drugs and methods for the regeneration of the central nervous system.
Summary of applications of nanotechnology in the treatment of Alzheimer's disease. (Image: Journal of Alzheimer’s Disease 13 (2008) 199–223, IOS Press)
Nanotechnology diagnostics approaches for Alzheimer's
Since the neurodegenerative process due to AD begins well before the disease's symptoms become apparent, early detection diagnostic tools must be highly sensitive and certainly less invasive than, say, a brain biopsy. Nazem and Mansoori argue that nanotechnology can be the basis of new tools for very early detection of AD because of their potential of detecting ultra-low concentrations of AD biomarkers, and potentially being able to detect multiple biomarkers simultaneously. "In addition, by targeting the specific pathology related biomarkers, nanotechnology tools can diagnose underlying AD pathology early and independent from brain reserve (the reserve capacity of the brain that enables people to tolerate the pathological changes that occur in the brains of people with AD)."
Bio-barcode assays and localized surface plasmon resonance (LSPR) nanosensors are mentioned as two methods for the cerebral spinal fluid (CSF) analysis for AD biomarkers. CSF has a higher degree of accuracy and can show brain tissue damages earlier than the known plasma biomarkers associated with AD. However, the in vitro CSF analysis requires the invasive procedure of lumbar puncture for obtaining a sample.
The authors write that nanotechnology has the potential to provide us with ultra sensitive in vivo detection methods (for instance with quantum dots, although their toxicity could make this approach problematic) of the AD biomarkers in plasma. They believe that the ultimate goal for very early detection of an underlying AD pathology would be the development of a safe and implantable nanoscale biosensor for prolonged monitoring of AD biomarkers in the CSF.
"Such a sensor must be able to transmit any biomarker detection event to an external device that records the transmitted signals and reports an estimated amount for the concentration of AD biomarkers in the CSF. Of course, in order to send such biosensor to a place exposing with CSF, it is necessary to design noninvasive approaches."
An eventual cure for AD will require therapeutics that cease the disease progress and will reverse its resultant damages. As Nazem and Mansoori point out, the general focus of therapeutic approaches in nanomedicine have been on drug discovery and monitoring, controlled release of therapeutic agents, and targeted drug delivery. "The current and envisioned applications of nanotechnology in neurology consist of neuroprotection, neuroregeneration, and drug delivery beyond the brain blood barrier."
While neuroregeneration treatments seem to be a considerable way out, and most likely will depend on effective stem cell technologies, neuroprotective applications could be available sooner and help in stopping or at least delaying the disease once diagnosed.
Designing therapeutic agents that protect neurons against cellular neurotoxicity is a prevention approach to protect against neuro-degenerative diseases such as AD. "Oxidative stress and amyloid induced toxicity are the two basic toxicity processes in AD pathogenesis. Anti-oxidant and anti-amyloid therapeutics are the focus of current drug discoveries against these toxicity processes."
Even if a potent drug for AD was available, its effective delivery into the brain would be a significant challenge thanks to the blood brain barrier (BBB), the tight seal of endothelial cells that lines the blood vessels in the brain and acts as a barrier to protect its cells. BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzymes) barriers and keeps most substances such as chemicals and large biomolecules out of the brain. The use of nanotechnology offers tremendous hope in the treatment of brain disorders by offering a way for drugs across the BBB (Nanotechnology improves the prospect of better treatment for brain disorders). Since a large portion of the AD pathogenetic mechanism happens inside brain cells, the nanoparticulate drug carriers no only must overcome the BBB but also be delivered into the target cells in the brain.
Without being able to give a time frame, of course, Nazem and Mansoori are confident that at some point in the future the increasing abilities offered by the combination of nanotechnology and some other novel approaches like stem cell technology could bring about a promising cure for Alzheimer's disease.