Could a blood test to diagnose Alzheimer’s disease be on the horizon?

Alzheimer’s disease is a degenerative brain disease characterized by the build up of “plaques” and “tangles” in brain tissue. Plaques are dense deposits of an abnormal protein called beta-amyloid eptide. Nerve fibre tangles are associated with another abnormal protein, the tau protein. These plaques and tangles are responsible for the death of nerve cells and the onset of symptoms typical of the disease.

According to the Alzheimer Society of Canada, the disease currently impacts more than half a million individuals in Canada, and this number is expected to double by 2030. In Canada alone, 348 new cases are diagnosed every day, and the financial burden of Alzheimer’s exceeds over $10 billion per year [5]

As a result, there is considerable anticipation for blood tests that facilitate early diagnosis of the disease. These tests typically measure fragments of the beta-amyloid protein (A-beta 42/40, SOBA), the tau protein (p-Tau 217, p-Tau 181), or neurofilament fragments indicative of degeneration (Nfl). What makes these blood tests particularly promising? Most currently available diagnostic methods either lack conclusive results or are too complex for widespread use in medical practice.

Current diagnosis of Alzheimer’s disease involves evaluating memory loss, decreased functional abilities and behavioural changes, all confirmed through medical imaging.

Medical imaging

Brain examinations using magnetic resonance imaging (MRI), computed tomography (CT scan) and positron emission tomography (PET scan) enable the detection of beta-amyloid plaque accumulation and the presence of tau proteins in the brain. These techniques also enable the differentiation of Alzheimer’s disease from other brain conditions that can manifest similar symptoms, such as age-related lesions or those resulting from strokes and brain tumours.

Cerebrospinal fluid analysis

The most dependable approach for measuring biomolecule levels associated with Alzheimer’s disease involves detecting beta-amyloid and tau protein residue in cerebrospinal fluid (CSF). However, obtaining CSF requires the insertion of a collection needle between two vertebrae in the lower back (lumbar puncture ), a complex procedure that involves local anesthesia.

Current blood tests

So far, blood tests employed in diagnosing Alzheimer’s disease have solely been utilized to exclude other conditions with symptoms resembling those of Alzheimer’s, such as hypothyroidism and severe vitamin B12 deficiency.

Genetic tests

Some genetic tests, including screening for abnormal versions of the apolipoprotein gene (APOE4), help assess an individual’s risk of developing Alzheimer’s disease. The presence of a single copy of this abnormal gene is believed to be associated with a two- to five-times higher risk of developing the disease, whereas with two copies of the gene, the risk could be 10 times higher!

However, genetic tests must be interpreted with caution, as many individuals carrying two copies of the APOE4 gene may never develop the disease, while those with no copies of the abnormal gene can still experience Alzheimer’s.

Tests can also be done on other genes (APP, PSEN1 and PSEN2) in families that have a hereditary form of Alzheimer’s. In this latter case, the disease manifests early (before age 65), unlike sporadic Alzheimer’s, which usually occurs after age 65. However, this hereditary form is rare, accounting for only about 5% of all Alzheimer’s cases.

Autopsy

A definitive diagnosis of Alzheimer’s can only be currently established through an autopsy that includes a microscopic analysis of the brain tissue of people who died from the disease.

There is currently no treatment for Alzheimer’s disease, but certain symptoms (e.g., mental function, behavioural changes) can be alleviated or slowed down through the use of medications. Approved several years ago, drugs such as donepezil, galantamine, rivastigmine, and memantine can alleviate symptoms of the disease by influencing the formation of acetylcholine or glutamate, molecules crucial for nerve signal transmission.

Recently, the pharmaceutical industry has introduced antibodies capable of neutralizing the beta-amyloid protein, preventing its deposition in the brain (Aducanumab, Gantenerumab, Lecanemab, etc.). Among these, Lecanemab (Leqembi®) has already received approval in the United States and has been under review by Health Canada since the spring of 2023.

When will blood tests be available ?

One of the new tests, based on beta-amyloid protein levels in the blood, the patient’s age, and the presence or absence of APOE4 gene copies, is already available in the United States. Its distinctive feature lies particularly in its relative simplicity combined with high diagnostic accuracy (94%) for early forms of Alzheimer’s disease. In some cases, this test could even establish a diagnosis before the typical symptoms of the disease appear or before accumulations of beta-amyloid plaques are detectable by a PET scan.

The push for these blood tests to be more widely accessible in Quebec and Canada is expected to intensify with the emergence of promising new antibody-based treatments, including the first whose approval is still pending by Health Canada. Blood tests will then facilitate early diagnosis of the disease, at a stage where possibilities for improvement would be more significant. However, a bit more patience is required: the first article demonstrating the effect of new antibody-based treatments is barely a year old [6].

This revised edition reflects an updated version from the original version published on January 13, 2020, on our website. We have incorporated recent facts to offer you current and pertinent information.