One of the primary characteristics of Alzheimer’s disease is the existence of neurofibrillary tangles in the brain. These asymmetrical protein clusters are closely linked to the development of illness. Researchers have now devised a method to identify them in their earliest stages. They hope this discovery will lead to early diagnosis and, as a result, better treatment outcomes.
Scientists have established a link between Alzheimer’s disease and the accumulation of particular proteins in the brain. However, the disease has already progressed by the time these proteins appear in brain scans, making therapy less effective.
Researchers at the University of Pittsburgh School of Medicine have discovered a biomarker that could help physicians identify the early warning signals of protein accumulation before it causes severe damage.
According to the new research, researchers created a biomarker test that can identify small quantities of tau protein prone to clumping and its misfolded pathological forms found in the brain, cerebrospinal fluid, and potentially blood years before tau tangles appear in brain scans of Alzheimer’s patients [1].
Nature Medicine published this research [2].
What are the Protein Hallmarks of Alzheimer’s Disease?
The two primary protein structures linked to Alzheimer’s are amyloid-beta plaques and neurofibrillary tangles (NFTs).
- Amyloid-beta: Amyloid precursor proteins aggregate to form amyloid-beta plaques as Alzheimer’s disease progresses, ultimately impairing brain cell function.
- Tau: Tau aids in maintaining the structural integrity of neurons in a healthy brain. This protein malfunctions and turns into NFTs in the brain of an Alzheimer’s patient.
The addition of phosphate groups to tau can cause it to become phosphorylated. While this is typical, the phosphorylation is aberrant or excessive in Alzheimer’s disease.
The term “hyperphosphorylated” refers to tau that has aberrant phosphorylation. This tau aggregates to create NFTs, which progressively accumulate inside cells, causing their death.
Studies indicate that elevated levels of hyperphosphorylated tau are linked to worsening Alzheimer’s disease cognitive symptoms [3].
The majority of efforts to find early indicators have been on amyloid-beta since it often enters the scene before NFTs. However, according to Thomas Karikari, Ph.D., the study’s senior author, a significant portion of individuals with brain amyloid-beta deposits would never experience dementia.
Put differently, it is not an effective biomarker. On the other hand, NFT levels in the brain are more closely correlated with disease progression.
Karikari explained that once a brain scan reveals tau tangles, it might be too late to stop the fire, and their cognitive function could rapidly decline.
These factors led the researchers to concentrate on identifying early indicators of NFT development in their search for a novel biomarker.
Recent Research: New Biomarker Test may Detect Alzheimer’s for Early
In the most recent study, using molecular biology and biochemistry methods, Karikari and his team discovered a core region of tau protein that is essential for neurofibrillary tangles production.
The “building blocks” of NFTs, including oligomers and protomers, which the researchers collectively call soluble tau assemblies, were the main emphasis.
There is very little known about the composition and function of these compounds. However, researchers do understand that the early stages of NFT creation are more harmful to brain cells than fully formed NFTs.
In their multifaceted investigation, the researchers first effectively measured soluble tau assemblies in brain samples from individuals who passed away from Alzheimer’s disease. The researchers then identified a critical stage in NFT development and phosphorylation sites that appear to be vital for NFT formation.
They demonstrated that these phosphorylation sites, known as p-tau-262 and p-tau-356, might be used as biomarkers for early illness since they could predict future NFT production.
The two new phosphorylation sites, p-tau-262 and p-tau-356, can reliably indicate the state of early-stage tau aggregation, which may be reversible with the right intervention.
According to Karikari, their test can detect tau tangle formation in its very initial stages, up to ten years before any tau clumps can appear on a brain scan.
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