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Alzheimer’s Disease: Do the “Eyes” Really Have It?

By: , Posted on: March 5, 2015

bursting neuronsAlzheimer’s is primarily a disease of the brain, although there is a correlation between retinal pathology and Alzheimer’s, as patients often exhibit poor vision and other visual signs of impairment. Diabetes, while an entirely different disease on the surface, is better known for its effect on the eye as well. Detailed comprehensive eye examinations are essential for all diabetic patients and, if left unchecked, diabetic retinopathy could lead to blindness.

Interestingly, the brain and the eye have similar anatomical vascular barrier structures referred to respectively as the blood-brain and blood-retina barriers.  Of note is that vascular pathological factors, such as hypertension, stroke, and high cholesterol, are common in both Alzheimer’s and diabetes.

As described in Chapter 14 of the newly released book, Bursting Neurons and Fading Memories: An Alternative Hypothesis for the Pathogenesis of Alzheimer’s Disease, a dysfunctional vascular barrier can lose its ability to keep restricted vascular components from entering the brain and eye.  For example, compromised blood-retina function through endothelial cell damage is observed before clinical evidence of retinopathy in diabetic patients.  Similarly, vascular pathologies in the brain precede the presence of plaques and cognitive impairments in AD mouse transgenic models. Therefore, dysfunctional blood-barrier function could be one of the earliest structural pathological events in these diseases.

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In recent studies, the level of beta-amyloid detected in the eye significantly correlated with the burden of beta-amyloid in the brain and allowed researchers to accurately identify people with Alzheimer’s.  Hence, amyloid detected in the eye may be an indicator of early Alzheimer’s.  Furthermore, the presence of amyloid in the eye not only suggests a dysfunctional blood-retina barrier, but also supports the alternative “Inside-Out” hypothesis (as defined in the aforementioned book). This theory suggests that the amyloid entering the neurons in the brain (leading to their demise) originates from the vascular system. In other words, Alzheimer’s is not a disorder solely originating in the neurons of the brain, as the prevailing hypothesis purports.

High resolution retinal scans can detect the presence of pale, fatty deposits on the retina, which are themselves signs of leaking blood vessels.  If the condition of blood-barrier health is similar in the eye and in the brain, and since imaging of the brain does not have high enough resolution to assess blood-brain barrier function, then the use high resolution scans of the retina could provide critical information to diagnose blood-brain barrier health.  If neuronal death is due to the leakage of amyloid out of the vascular system into the brain (“Inside-Out” hypothesis), then restoring vascular health could prevent Alzheimer’s.

Read more about Michael’s Alternative “Inside-Out” of Neuronal Death in Alzheimer’s here.

About the Book:

Advances in Alzheimer’s disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons.

However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field’s best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory.

9780128019795Reviewing many scientifically peer-reviewed publications, Bursting Neurons and Fading Memories in Alzheimer’s Disease describes the “Inside-Out” hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons.

Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development.

If you are interested in further understanding of the details and evidence of this alternative approach, the book is available on the Elsevier Store. Use discount code “STC215″ at checkout and save up to 30% off the list price.

About the author:

 Michael R. D'AndreaMichael R. D’Andrea received his PhD in Cell and Developmental Biology and his MS in Molecular Biology at Rutger’s University, New Brunswick, NJ, and his BA in Psycho-Biology at Western Maryland College, Westminster, MD. His dissertation work utilized molecular and histological assays to study the regulation of DNA topoisomerases in human cancers. His earlier career concerned the use of the high magnification electron microscopy to support oncogenesis in preclinical models, and then moved into a new field where he and his peers co-invented the chorionic villus sampling method at Thomas Jefferson for clinical chromosomal analysis. In the late 1980s and early 1990s, he mastered immunohistochemical methods at the light and electron microscopy levels when he began publishing his work in scientific journals.

However, it wasn’t until the mid-1990s, while working at Johnson & Johnson’s Pharmaceutical Research & Development as the Target Validation Team Leader, did he become engaged in Alzheimer’s disease (AD) research. His Team was responsible for supporting target discovery and validation, while supporting biomarker discovery in preclinical and experimental models using genomic, proteomic, and histopathological methods across many therapeutic areas and was honored with over a dozen Leadership and Scientific awards. Currently, he has over 100 scientifically peer-reviewed scientific publications and invited reviews, about a third of which concern the neuropathology of AD, and holds 11 scientific patents. He has reviewed hundreds of papers for many scientific journals, reviewed international grants in the AD field, and is currently on the editorial board of the journal, Biotechnic & Histochemistry.

He has been invited to speak at numerous International, National, and Regional meetings, as well as at Universities and other companies to discuss his novel observations concerning the origin of amyloid plaques, the existence of various plaque types, and most recently that AD is also an autoimmune disease; all of which is presented in this book. Recently, Michael established a contract research company, Slidomics, LLC ( to apply his histopathological and target validation expertise by providing high quality data and analysis much like what you see in this book.

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