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Alzheimer's and related dementia research

Causes and Diagnosis

Possible Causes of Alzheimer’s

Aging – while this may seem too broad, it is important to note that Alzheimer’s has not been diagnosed in anyone under 27 years of age and in very few under age 50. Something changes (or lots of things change) until, by some estimates, half of us who manage to live past 85 will have some form of dementia.

Amyloid-Beta Plaques – First a tiny bit of biology (because that’s all I know).  Amino acids are the building blocks of life.  Strung together in sequence they form peptides.  If more than 50 amino acids are in sequence then we have a protein.

The brain produces a protein called Amyloid Precursor Protein (APP) that is severed into a shorter chain (a peptide) by two different enzymes (secretase beta and gamma). Secretase beta (which has a lot of different names) is produced by the BACE1 gene as part of the normal process of producing sheaths for nerve cells.

It is generally accepted that in Alzheimer’s these amyloid beta peptides become misfolded or tangled and form a plague on and in the brain that is damaging. The result is the hallmark symptoms of Alzheimer’s Disease. The head scratcher is that some people develop amyloid beta plagues, but do not develop Alzheimer’s.

Inflammation – is a biological response to harmful stimuli, such as pathogens, damaged cells, or irritants.  Inflammation is a necessary element of the immune response and is normally closely regulated by the body, but when the inflammatory signals fails to switch off “chronic inflammation” results.

Chronic and even acute inflammation may be responsible for dementia, although it is not certain if it is a cause, contributor, or secondary phenomenon.

Tau tangles – Tau is a protein (more than 50 amino acids strung together) and is produced by a single gene located on the 17th chromosome. Officially called MAPT for Microtubule-Associated Protein Tau, the protein is crucial for the formation of a sort of scaffolding or framework to support the micro tubes that make up neurons. When these proteins misfold or tangle, the scaffolding becomes a mess that reduces or eliminates the functioning of the neuron.

Like the Beta Amyloid Plagues mentioned above, these tangles are often found in the brains of those with Alzheimer’s and one type of tangle may induce the other, although we don’t know if that is true or even which tangle comes first.

Oxidative Stress – a theory of aging in general first proposed by Denham Harman in 1956.

Let’s start with the cell and let’s also agree to grossly oversimply everything. Inside our cells are little substructures called organelles. One such organelle is the Mitochondrion (singular). Very few of our cells have no mitochondrion, while most have several mitochondria (plural) and our liver cells have lots and lots of mitochondria.

Mitochondria consume oxygen and produce ATP (adenosine triphosphate) which is our main source of chemical energy.  This low level combustion produces heat and toxins, two of which (peroxides and free radicals) damage pretty much anything in their path (proteins, fats, and DNA included).  Antioxidants in our cells combine with the free radicals and neutralize them.

We naturally produce the antioxidant glutathione and several others are acquired through diet such as vitamins A, C, and E.  When there are more toxins than antioxidants to neutralize them cells and their components become irreparably damaged.

 

Methods of Diagnosis

Sadly, by the time Alzheimer’s symptoms are pronounced enough for a diagnosis to be made with confidence, the damage has been going on for years. It is the accumulation of harm, like a river eroding rock, that eventually manifests in the collection of symptoms that we call dementia.

The goal of research has been to diagnose Alzheimer’s earlier in the process. While there is still no cure per se, there have been promising results for slowing the progression and in some cases maybe even reversing the disease. If Alzheimer’s could be identified years before symptoms emerge, the likelihood of slowing or stopping it increases dramatically.

The following are largely potential new methods of diagnosing Alzheimer’s and their corresponding articles.

Blood Test – None currently available. In 2017 Ohio State University reported the development of a blood and/or spinal fluid test that combined with an algorithm was able to determine both a diagnosis of Alzheimer’s and the stage of the disease. The test looked for Amyloid Beta proteins. Then using the binding properties of antibodies found that those with the disease had stiffer and more clustered Aß proteins.

PET Scan – Currently, the only way to detect amyloid beta in the brain. Expensive and not widely available. Positron-emission tomography (PET) detects pairs of gamma rays emitted by a tracer that is typically injected into your bloodstream or the area of the body to be studied. The PET scan will produce lovely 3D images with the help of a computer.

Retinal Scan – Cedars-Sinai, working with NeuroVision Imaging, developed a non-invasive retinal scanner that could detect beta-amyloid plaques in the retina. They gave patients curcumin, the bright yellow chemical in turmeric, because it binds well with beta-amyloid plaques, can cross the retinal barrier, and is a natural fluorochrome that generates a florescent signal making the plaques light up.

The study found beta-amyloid plaques in the retinas of live test subjects and in amounts correlated with the plaques found in their brains as verified by PET scans.

Sniff Test – One of the first places in the brain to degenerate in people with Alzheimer’s disease is the front part of the temporal lobe.  That’s the area involved with the smell system and with forming new memories.

Researchers at the University of Pennsylvania in 2016 used the Sniffin’ Sticks Odor Identification Test and reported a simple “sniff test” can enhance the accuracy of diagnosing Alzheimer’s and “appears to be useful for diagnosing a pre-dementia condition called mild cognitive impairment (MCI), which often progresses to Alzheimer’s dementia within a few years.”

An inexpensive version reported in 2013 is called the “peanut butter test” and could be performed at home if you can keep the dog away long enough to finish the test.

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