Alzheimer Diagnosis

Overview

Dr. Campbell Using the Imaging System
Campbell's Lab is developing an early diagnosis system for Alzheimer's disease by optical imaging. We see the retina as a window for the brain to relay information. We want to overcome the limitation of definitive diagnosis of Alzheimer's only after death.

We characterized deposits of amyloid beta in the neural layers of the retina between patients with Alzheimer's and those without. We are now developing a non-intrusive optical technique of imaging the deposits in the living eye to allow for early diagnosis.

We expect to test our method in 2 to 3 years in the living human eye. It will be more accessible, less expensive, and more feasible than the current brain imaging in Alzheimer's disease.

Dr. Campbell talks about the lab's work during Alzheimer's Awareness Month.

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Alzheimer's Disease

Alzheimer's disease is a devastating form of dementia that afflicts nearly 26 million people worldwide1. Alzheimer's is an age-related neuro-degenerative disease which deteriorates brain tissue. It severely affects the patient's quality of life and has a negative impact on the caretakers' lives2. Alzheimer's disease disturbs sleep cycles3 and disrupts memory and learning abilities. In later stages, a patient loses the ability to control basic life functions and cannot live independently.

The disease is characterized by over-accumulation of amyloid-β4, a protein sub-unit within the brain. This protein is always present in small quantities in its simplest monomer form. However, in Alzheimer's, the molecules form aggregates to create dimers (and trimers) which are toxic to the nerve cells of the brain4. Eventually, large plaques deposits and tangles are the main forms of diagnosis after death 5,6.

Currently, definitive diagnostics tests for Alzheimer's are not readily available, and can be expensive and costly. Positron emission tomography (PET) has been used by medical physicists to image amyloid-β in real-time7. Nevertheless, better tests are required for early detection and treatment, as well as the tracking of new treatments8.

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The Eye as a Window for the Brain

OCT System
A reoccurring theme of the research in Campbell's Lab is seeing that the eye is a window to the brain. Alzheimer's is no exception. Mice models have been shown to have amyloid-β in the retina, particularly in the nerve fiber layer (NFL)8. The transparency of the retina makes it feasible for high-resolution optical imaging7. We aim to image amyloid-β in vivo in the human eye to create an accessible and inexpensive diagnosis for Alzheimer's.

Campbell's Lab specializes in high-resolution live optical imaging of the retina. The non-invasive diagnosis system would include adaptive optics to correct for the aberrations of the eye. Furthermore, fluorescence imaging and optical coherence tomography (OCT) are important to image the eye. We previously designed, with collaboration from Physical Science Inc., a novel adaptive optics imaging system to detect early changes in the retina for type 1 diabetes. This system can be modified to allow for Alzheimer's Disease diagnosis. The image on the right shows some components of our optical system and its applications with a user.

In order to detect amyloid-β, we study the interaction of light with the deposits and the surrounding tissue and examine the returning wave. A second method takes advantage of spectroscopy. By measuring different absorbance wavelengths, we are able to determine the characteristics of a layer. Amyloid-β deposits are expected to contain a different signature characteristics than the surrounding tissue.

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References

  1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s Disease. Alzheimers Dementia 2007(3),186-191.
  2. Alzheimer’s Society of Canada. Rising Tide: The Impact of Dementia on Canadian Society. 2010.
  3. Nieoullon A, Bentué-Ferrer D, Bordet R, Tsolaki M, Förstl H. Importance of circadian rhythmicity in the cholinergic treatment of Alzheimer's disease: focus on galantamine. Curr. Med. Res. Opin.  2008, 24(12), 3357-3367.
  4. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992, 256(5054), 184-185.
  5. Liu L, Orozco I, Planel E, Wen Y, Bretteville A, Krishhamurthy P, et al. A transgenic rat that develops Alzhiemer’s disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment. Neurbiology of Disease. 2008, 31, 46-57.
  6. Quigley H, Colloby SJ, O'Brien JT. PET imaging of brain amyloid in dementia: a review. Int. J. Geriatr. Psychiatry. 2011, 26(10), 991-9.
  7. Mosconi L, Verti V, Glodzik L, Pupi A, De Santi S, de Leon M.  Pre-Clinical Detection of Alzheimer’s Disease Using FDG-PET with or without Amyloid Imaging. J. Alzheimers Dis. 2010, 20(3), 843-854.
  8. Weiner M, Aisen P, Jack C Jr, Jagust W, Trojanowski J, Shaw L, et al. The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans. Alzheimer’s & Dementia. 2010, 6, 202-211.

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