Abnormal alterations in beta-amyloid and tau proteins drive the onset and progression of Alzheimer's disease, according to neurological experts and clinical researchers.
Alzheimer's disease is the most prevalent neurodegenerative disease globally and stands among the top ten causes of disability, dependence, and mortality worldwide, said Raquel Sánchez del Valle, coordinator of the Behavior and Dementias Study Group of the Spanish Society of Neurology. She noted that the condition primarily affects people over 65 years of age and warned that the aging global population will make Alzheimer's the leading cause of projected increases in dementia cases.
The disease causes progressive cognitive decline that interferes with everyday activities. Its primary characteristic is memory loss, which is accompanied by misplacing objects, mood and behavioral changes, spatial and temporal disorientation, attention loss, and difficulty executing complex thoughts such as reasoning or planning.
Protective functions of beta-amyloid
Although the exact causes of Alzheimer's remain incompletely understood, researchers know that the beginning of the disease relates directly to abnormal behavior by beta-amyloid and tau proteins. Under normal physiological conditions, both proteins perform vital functions in brain health before becoming altered.
Beta-amyloid is a protein fragment created when a larger molecule, known as amyloid precursor protein, is divided into smaller components. Amyloid precursor protein is found in many parts of the body, particularly within connections between neurons.
In healthy brains, beta-amyloid performs protective roles. Medical experts from health services company Sanitas explained that beta-amyloid protects neurons against oxidative stress caused by free radicals, helps regulate cholesterol levels, and defends the brain against pathogenic microorganisms such as bacteria, fungi, and viruses.
The protein also activates enzymes responsible for transmitting signals within neurons and provides the glucose required for neuronal function. Sanitas specialists stated that when functioning correctly, beta-amyloid keeps neurons protected from damage, secures their energy supply, and facilitates communication between cells.
Accumulation of toxic protein structures
Under normal conditions, beta-amyloid is eliminated once it is no longer needed. In people with Alzheimer's, however, the protein accumulates into harmful structures that disrupt communication between neurons. Sanitas experts emphasized that the core problem is not the presence of beta-amyloid, but an imbalance in the system of production and elimination.
When beta-amyloid accumulates in excess, it forms distinct structures that carry increasing levels of toxicity for neurons. The first structures to form are monomers. Monomers are not toxic on their own, but when produced in large amounts, they begin to bind together. Sanitas specialists highlighted that this aggregation serves as the first warning sign that cellular balance has broken down.
Monomers join to form oligomers, which then aggregate further to create larger structures known as fibrils and plaques. The presence of fibrils and plaques indicates that the neurodegenerative process is already far advanced. Sanitas experts expressed that all of these aggregates progressively alter the energy power plants of neurons, depriving them of the fuel needed to communicate and function properly.
Functions and failure of tau protein
Tau protein is also closely linked to Alzheimer's and is essential for communication between neurons as well as internal cellular functions. Tau maintains the structure of microtubules, which serve as internal pathways for transporting vital materials inside neurons. Tau binds to microtubules to stabilize them against deformation.
The protein also regulates axonal transport. Sanitas specialists explained that the axon is the long extension of the neuron that transmits electrical impulses. Tau enables essential substances to travel from the cell body to the end of the axon, where connections with other neurons take place.
Additionally, tau participates in forming new neurons and contributes to synaptic plasticity, which refers to the brain's capacity to adapt, learn, and form new memories across neuronal connections called synapses. Tau also shields neurons against cell damage and death, helping them resist stress and preventing degeneration.
In patients with Alzheimer's, tau changes its normal shape and undergoes a process called hyperphosphorylation. When hyperphosphorylated, tau aggregates into tangles that block internal traffic of essential materials, alter gene function within neurons, and trigger inflammatory processes. As more tangles accumulate and spread across the brain, nervous system function worsens and the disease advances.
Blood biomarker detection for early diagnosis
Tau protein is present in the blood of all individuals, but non-affected individuals maintain very low and stable concentrations. In contrast, levels of phosphorylated tau, specifically forms designated as p-tau181, p-tau217, and p-tau231, rise in both blood and cerebrospinal fluid as Alzheimer's progresses.
Medical professionals can now measure tau levels using a standard blood test. A clinical study led by researchers from the Barcelonaßeta Brain Research Center and the Hospital del Mar Research Institute, alongside the University of Gothenburg and Lund University in Sweden and the University of Brescia in Italy, validated the detection of the phospho-tau 217 biomarker in blood to assess Alzheimer's risk in people with symptoms of cognitive decline.
The study analyzed the biomarker's utility in 1,767 patients from Hospital del Mar in Barcelona, the Hospital of Brescia, the Hospital of Gothenburg, the Hospital of Malmö, and a primary care center in Sweden.
Marc Suárez-Calvet, a researcher at the Barcelonaßeta Brain Research Center and neurologist at Hospital del Mar, explained that detecting this biomarker allows doctors to determine which patients need to undergo further diagnostic procedures, such as a lumbar puncture or PET scan, and which patients do not, enabling accurate detection of Alzheimer's in its initial phases.
