Diagnosing Alzheimer’s Disease like looking at a Clothing Tag

What kills more people, Alzheimer's or Breast Cancer? You may be surprised that Alzheimer's is the answer to this question as it is becoming one of the most prominent causes of death in the US.

The need for research on how to treat Alzheimer's is becoming necessary. As Alzheimer's is a rising epidemic in the US, and as it is a terminal disease, a cure is becoming even more relevant as the global population over the age of 65 is currently growing faster than any other age group and expected cases of AD are expected to sky rocket in the next thirty years. 

Alzheimer's disease is known as a neurodegenerative disease and is the most predominant cause of dementia. Several million people worldwide suffer from Alzheimer's disease (AD). 

The two types of AD are early-onset Alzheimer's and late-onset Alzheimer's. Late-onset Alzheimer's contributes to 85% to 90% of all AD cases as it is common in 50% of adults above the age of 85. Early-onset Alzheimer's is much less common making up only 10% to 15% of all AD cases and is most associated with familial origin (genetic factors). People with Early-onset Alzheimer's also get diagnosed with the disease earlier than the age of 65.

Visual representation of the progression (Stages) of Alzheimer's Disease.

A reliable diagnosis for AD has yet to be discovered, but there are 3 categories of tests used to determine the progression of AD. Blood tests and imaging provide patients suffering with AD the most non-invasive and easily accessible tests, however they have less disease-sensitive biomarkers. Cognitive changes have been the only form of reliable assessments in the variable symptoms AD impairs the brain with.
Now, what is a biomarker? A biomarker is best defined by the National Institutes of Health Biomarkers Definitions Working Group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”.

Detailed review of current medical standards on diagnosis Categories and Markers that identify with AD.

The biomarkers associated with AD can metaphorically be described as clothing tags dropped from a shirt after a robbery, providing details on what type of clothing was stolen (what specific biomarkers) and where the clothing may have come from (what parts of neurons/CSF fluid/plasma the markers originated from). The most recognizable biomarkers that connect to AD include amyloid beta plaques (clumps of amyloid beta, APP) which come from trans-cellular proteins in the cell membrane of the neuron and neurofibrillary tangles which come from intracellular tau proteins in microtubules inside the neuron.

Visual representation of neurofibrillary tangles and beta amyloid plaque that create problems in Neuron communication and lead to Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD).

CSF biomarkers, which come from cerebrospinal fluid, are tested using lumbar punctures which take a small amount of the one pint of cerebrospinal fluid (CSF) you have in your brain and spinal cavity. The types of biomarkers which come from this lumbar puncture would contribute to an AD diagnosis are APP (known as amyloid beta plaques, in the forms of Aβ40/42 and truncated Aβ) and tau proteins (in the form of CSF-Tau). Instead of having to observe the effects of these biomarkers over time in the form of symptoms (neurodegenerative cognitive impairments), performing minimally invasive procedures to observe these biomarkers before they show in the form of symptoms can help drastically understand what might be occurring in patients. An earlier diagnosis allows doctors, patients, and their family to prepare themselves and prescribe modified drugs that can positively affect the future of the patient and the progression of the disease.

Although research is advancing in this field, the accuracy of drugs and tests are still being determined as AD is a multifactorial neurodegenerative disorder, making pinpointing several factors and progressions of the disease difficult to achieve.