Before extensive research was conducted, Alzheimer’s disease could only be confidently diagnosed after death.
Medical professionals would examine the brain for physical changes, such as protein plaques and tangles, under a microscope.
But now, the possibility of diagnosing dementia from a simple blood draw when symptoms first appear is becoming more realistic.
Researchers are measuring protein accumulations in the blood, known as biomarkers, to track brain pathology early on and identify those at risk of developing dementia later in life.
However, more research is needed to understand the relationship between blood biomarkers and dementia risk better. Most biomarker studies have focused on older adults and have not followed individuals over time to see when these biomarkers appear or how they change from midlife to late life.
Alzheimer’s disease and related dementias are influenced by factors such as age, genetics, and co-morbidities.
To develop an accurate blood test for Alzheimer’s and other dementias, researchers need to fill gaps in their understanding of biomarker trends and other factors driving disease progression. This knowledge could help prevent the disease and preserve brain health.
Dr. Priya Palta, an associate professor of neurology and an expert in cardiovascular disease, aging, and dementia, said, “There is a shortage of research on blood biomarker changes in individuals in their mid- to late-life, especially in diverse community-based cohorts, and on the relationships between biomarker changes and midlife cardiometabolic disorders.”
“Understanding these biomarker relationships could provide further insights into how we can help maintain brain function in people at risk for dementia, monitor disease progression, or identify individuals who may benefit from treatment,” she added.
A team from the University of North Carolina School of Medicine, New York University Grossman School of Medicine, and Johns Hopkins University found that certain blood biomarkers of Alzheimer’s disease pathology and neurodegeneration in midlife and late life were strongly associated with late-life dementia.
Their results were published in JAMA, accompanied by an editorial discussing the findings.
Several biomarkers in the blood reflect the Alzheimer’s disease process, where toxic proteins accumulate, causing damage, inflammation, and neuron death in the brain. Tau is one of the two hallmarks of Alzheimer’s used to diagnose the disease postmortem.
It supports and transports materials within neurons. In Alzheimer’s, tau undergoes a change called phosphorylation, measurable as Phosphorylated tau-181 (p-tau181), leading to neurological tangles in the brain.
Another hallmark, Amyloid-beta (Aβ) peptides 42 (Aβ42) and 40 (Aβ40), are prone to aggregate and deposit in the brain as amyloid plaques.
These proteins primarily accumulate in the brain, reducing their levels in the spinal cord and blood vessels. A low ratio of Aβ42/Aβ40 is an early indicator of Alzheimer’s pathology.
As these proteins accumulate, neurons are damaged and die, leading to neurodegeneration. Neurofilament light chain (NfL), a structural component of neurons, breaks off when neurons are damaged, entering the cerebrospinal fluid (CSF) and bloodstream.
High NfL levels are a key early indicator of neuronal damage and disease, often rising before dementia symptoms appear.
Inflammation in the brain, another common feature of Alzheimer’s and related dementias, is triggered by neuronal damage. When neurons are inflamed, astrocytes in the brain release Glial Fibrillary Acidic Protein (GFAP) into the CSF and bloodstream.
Researchers used data from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), which recruited middle-aged adults in the late 1980s. Originally focused on atherosclerosis, ARIC-NCS now connects cardiovascular risk and dementia.
The team analyzed data from 1,525 ARIC-NCS participants, examining prior clinical information and stored blood samples, as well as demographic data, such as race, age, and education level.
The study found that the Aβ42/Aβ40 ratio decreased with age, while p-tau181, NfL, and GFAP increased, indicating neurodegeneration.
Midlife hypertension and diabetes were linked to a more rapid rise in NfL and GFAP. Overall, the study determined that all blood biomarkers in late life had a strong association with late-life dementia.
These findings show that disease-related changes can be identified in the blood nearly 20 years before dementia symptoms emerge. However, more work is needed to identify specific biomarkers for diagnosing Alzheimer’s and related dementias at an early stage.
This study highlights the importance of monitoring blood biomarkers for Alzheimer’s disease-related pathology and neurodegeneration in assessing dementia risk.
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The research findings can be found in JAMA.
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