Study detects biomarker changes nearly 30 years before symptom onset of Alzheimer’s disease NatureMedicine EmoryMedicine harvardmed biomarker Alzheimers Alzheimersdisease disease
By Dr. Liji Thomas, MDAug 10 2023Reviewed by Sophia Coveney A new paper, recently published in Nature Medicine, has shown how Alzheimer’s disease pathology comes into being over a period of almost three decades.
Autopsy studies have shown how brain tissue changes its attributes, at all levels, but biomarkers remain essential to track the course of such alterations over the lifespan, especially while the individual remains young and healthy, and in those who never develop symptoms of dementia at all. What does the study show? The researchers found that changes in secreted and excreted proteins in the CSF reflect the earliest steps in AD pathology.
These proteins, including Aβ, associate with each other via their common ability to bind heparin, which facilitates plaque formation. The Christchurch APOE mutation knocks down this heparin-binding capacity and is associated with markedly lower susceptibility to ADAD. So is the APOE ε2 allele that protects against late-onset AD and binds heparin at reduced rates.
Successive changes were then observable in other categories of biomarkers, beginning 26 years before the onset of symptoms and involving the 14-3-3 family of proteins that are expressed at neuronal synapses. About 10 years later, this was associated with a rise in NEFL, indicating the slow progression of changes in brain axons and white matter metabolism. This is the third category of changing markers.
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