Alzheimer’s disease memory decline is predicted by the accumulation of tau in the brain early in the disease’s progression

Researchers at Karolinska Institutet compared the accuracy with which different Alzheimer’s disease biomarkers predicted the progression of the disease and its effect on the ability to remember.

Using a PET scanner, the researchers discovered that early accumulation of tau proteins in the brain was more effective at predicting memory impairment than biomarkers in the cerebrospinal fluid or amyloid plaque in the brain. According to the findings, which were published in the journal Molecular Psychiatry,


Dementia affects more than 50 million people worldwide, a staggering number. As the most common form of dementia, Alzheimer’s disease (AD) is characterized by an accumulation of the proteins beta-amyloid (A) and tau in the brain, which is followed by a progressive decline in memory over time. The pathological progression can manifest itself in a variety of ways, and it is difficult to predict how quickly the symptoms will manifest themselves in any given individual. A person’s brain may contain amyloid plaque, which is not necessarily indicative of the development of Alzheimer’s disease.


Biomarkers are being developed at a rapid pace


According to study first author Marco Bucci, a researcher at the Center for Alzheimer Research, which is part of the Department of Neurobiology, Care Sciences, and Society at Karolinska Institutet, “a rapid development of different Alzheimer’s biomarkers has occurred in recent years, enabling us to measure and detect early signs of the disease in patients.” In order to improve not only the diagnosis but also the prognosis and treatment of the disease, researchers must develop tests that are more specific in their ability to predict the development of the disease.


A number of biomarkers are used to detect the presence of A or tau deposits, while others are used to assess the level of nerve function loss (neurodegeneration). Protein accumulation and neurodegeneration can be detected in the cerebrospinal fluid (CSF) and plasma, as well as through brain imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), among others (MRI). The interchangeability of brain imaging methods and analyses of CSF biomarkers (pTau and A) is recommended by current guidelines for the early detection of Alzheimer’s disease with biomarkers, but this has been questioned. There is also a scarcity of longitudinal studies that demonstrate how the biomarkers are linked to the progression of cognitive decline.


High levels of tau are associated with memory impairment


‘Our study demonstrates that the presence of amyloid plaque in the brain, as well as changes in A and pTau concentrations in the CSF, can be detected early in the course of the disease, but that these findings do not appear to be associated with later memory loss,’ says Dr. Bucci. In contrast, the presence of tau protein in the brain, as measured by a PET scanner, is associated with a rapid decline in cognitive function, particularly in episodic memory (which is frequently affected at an early stage of the disease).” “Based on our findings, tau PET should be recommended for the clinical prognostic assessment of cognitive decline in Alzheimer’s patients,” the researchers conclude.


Using brain imaging (PET and MRI) as well as CSF analysis, the researchers discovered that a group of 282 participants, consisting of people with mild cognitive impairment, people with Alzheimer’s dementia, and healthy controls had lower levels of the neurotransmitter dopamine. 213 of the participants were also tested for episodic memory over a three-year period, which was done on them (i.e. short term memory related to daily events).


It is possible to become a drug target

“Our findings demonstrate that the concentration of tau in the brain of people with Alzheimer’s disease plays an important role in the disease’s pathological progression and that tau may become a key target for future drug treatments,” says principal investigator Agneta Nordberg, professor at the Karolinska Institutet’s Center for Alzheimer Research.

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