New understandings of Alzheimer's have emerged

Harold Mandel's picture
An image of the brain

Alzheimer's disease is a dreaded disease which is associated with aging. An irreversible downhill course in cognitive functioning with loss of ability to care for oneself is a hallmark of this illness. In order to make more effective prevention and earlier intervention with more effective treatments possible for Alzheimer's disease aggressive research has been ongoing.

A part of the brain known as the entorhinal cortex has been implicated in the early stages of Alzheimer's disease, reports Nature Neuroscience. Changes have been observed in the tau protein and in the cleaved fragments of the amyloid precursor protein (APP) in this area of the brain in victims of Alzheimer's. This has been studied with high-resolution functional magnetic resonance imaging and mouse models.

Columbia University researchers have showed where Alzheimer's starts and how it spreads using high-resolution functional MRI imaging in patients with Alzheimer's disease and in mouse models of the disease, writes Columbia University Medical Center in research released to the public on Dec. 22, 2013. The Columbia University Medical Center researchers have clarified three fundamental issues about Alzheimer's, including:

1: Where it starts

2: Why it starts there

3: How it spreads

Aside from helping to advance an understanding of Alzheimer's, these findings may help improve the early detection of this disease at a time when drug therapy may be most effective. Scott A. Small, MD, a neurologist and one of the authors of this research paper, has said, “It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex.” However, this study has been the first to demonstrate in living patients that Alzheimer's begins specifically in the lateral entorhinal cortex, or LEC. The LEC has been observed to be a gateway to the hippocampus, which plays a vital role in the consolidation of long-term memory, and other functions. When the LEC is affected, other aspects of the hippocampus are also affected.

It has been demonstrated in this study that Alzheimer's spreads over time from the LEC directly to other areas of the cerebral cortex, including in particular, the parietal cortex. The parietal cortex is a brain region involved in various functions, which includes spatial orientation and navigation. It is suspected by the researchers that Alzheimer's spreads functionally, meaning by compromising the function of neurons in the LEC. This then leads to the compromising of the integrity of neurons in adjoining areas.

It has also been discovered that LEC dysfunction occurs when there are changes in tau and amyloid precursor protein (APP) together. Karen E. Duff, PhD, one of the authors of this study, said, “The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's.” A large group of healthy elderly individuals was followed in this study, some of whom have gone on to develop Alzheimer's disease. There was a unique opportunity to image and characterize patients with Alzheimer's in its earliest, preclinical stage in this study.

There were 96 adults followed for an average of 3.5 years in this study. Over this time 12 of the subjects were found to have progressed to mild Alzheimer's disease. A careful analysis of the baseline MRI images of those 12 patients showed significant decreases in cerebral blood volume, which is a measure of metabolic activity, in the LEC in comparison with that of the 84 adults who were not suffering from dementia.


The second part of this study focused on the role of tau and APP in LEC dysfunction. It was not previously known that tau and APP abnormalities interact to drive the dysfunction associated with Alzheimer's disease. This association was found in particular in preclinical Alzheimer's. To study this phenomenon, the researchers created three mouse models:

1: One with elevated levels of tau in the LEC

2: One with elevated levels of APP

3: One with elevated levels of both proteins

It was discovered by the researchers that the LEC dysfunction occurred only in the mice with both tau and APP. This study has significant implications for both research and treatment.

Dr. Small has said, “Now that we’ve pinpointed where Alzheimer's starts, and shown that those changes are observable using MRI, we may be able to detect Alzheimer's at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions.” Furthermore, the researchers say the new imaging method may be able to be used to assess the efficacy of promising Alzheimer's drugs during the early stages of the disease.

With Alzheimer's disease we are dealing with a type of dementia which causes problems with memory, thinking and behavior, writes the Alzheimer's Association. The symptoms of this disorder generally develop slowly and worsen over time. Eventually the symptoms become severe enough to interfere with daily tasks. This is the most common form of dementia.

Dementia is a term used to refer to memory loss and loss of other intellectual abilities which are serious enough to interfere with daily life. About 50 to 80 percent of all dementia cases are due to
Alzheimer's disease. This is not a normal part of the aging process. However, the greatest risk factor for Alzheimer's is aging. The majority of people who suffer from Alzheimer's are 65 years old and older. There is also an early onset variant of this disorder which hits people in their 40s and 50s seen in up to 5 percent of people with the disease.

Alzheimer's is a chronic progressive disease which worsens over time. The symptoms of dementia gradually worsen over the years. Memory loss is mild in the early stages of the disease. However, in the late stages of the disease people lose the ability to carry on a normal conversation and to respond to their environment in normal manners. Alzheimer's ranks as the sixth leading cause of death in the United States.

Most Alzheimer's patients live an average of eight years after their symptoms become noticeable to other people. Treatments which are presently available for Alzheimer's cannot stop the disease from progressing, but they can temporarily slow the worsening of dementia symptoms and improve quality of life for people suffering from this illness. I have reported on findings that magnesium may help prevent mental decline in a separate article for EmaxHealth.

Along with millions of other people I was put in a state of shock when past President Ronald Reagan was diagnosed with Alzheimer's disease. To witness a vibrant elderly person who demonstrated just how much someone could still accomplish in life as he ages, fall so quickly into a vegetative state of existence, heightened my sensitivities and concerns about Alzheimer's. Over the years I have listened to stories about how this disorder stresses families to the limit due to the problems associated with care giving for sufferers of this disease. And I have felt completely helpless to assist in any significant manners each time I have been confronted with a victim of this illness.

I therefore fully support larger investments in research aimed at cracking the riddle of Alzheimer's disease. Our goal must be to prevent and cure this tragic disorder. In another article for EmaxHealth I have written about findings that omega-3 fatty acids may help prevent and treat Alzheimer's.



Like to be kept informed of new findings concerning Alzheimer's disease
It would be a reasonable assumption to think that reducing APP is a good approach to treating Alzheimer's. If so, then taking high dose fish oil is good place to start.