preclinical marker of Alzheimer’s

Researchers are continually looking to find out more about Alzheimer’s disease to identify its presence earlier and improve treatment. A new study identifies white matter alterations as a potential preclinical marker of Alzheimer’s disease, which could improve attempts at disease prevention.


Alzheimer’s disease (AD) is a long, progressive mental deterioration that leads to loss of memory and thinking skills at an old age. With new advancements in medical technology, clinicians are able to identify more markers for disease, allowing for earlier detection and treatment. The hope is that treating AD earlier will lead to greater success in preventing the dementia and neural degeneration the disease causes.

Alzheimer’s begins far before the onset of dementia, with neural degeneration occurring prior to becoming symptomatic. Though the originating cause is still unclear, scientists have identified changes in brain matter consistent across cases of AD. White matter, which is responsible for the transport of information throughout the brain, undergoes microstructure alterations and losses in volume. Additionally, specific proteins undergo increases in concentration when the disease is present. Newly developed MRI measures allow researchers to more sensitively analyze parameters that may be related to Alzheimer’s, creating potential for earlier detection.

In their study published in Journal of the American Medical Association Neurology, Dean III et al. used cerebrospinal fluid (CSF) collection and a new MRI technique to investigate predicted markers of preclinical AD. Three proteins that are markers of AD pathology were measured: Aβ42, Ttau and Ptau, and compared against changes in white matter content such as myelin water fraction (MWF). 71 asymptomatic participants between 48 and 72 years of age underwent neurological, genetic and laboratory testing and statistical analysis was run to determine associations between the AD marker proteins and white matter content. The researchers hypothesized decreased Aβ42 (reflecting an increase in detrimental protein deposits in the cortex), increased Ttau (reflecting increased neurodegeneration), and increased Ptau (reflecting increase in neurofibrillary tangles), would be associated with a decrease in MWF.

Using new quantitative measures from CSF collections and MRIs, researchers were able to identify significant associations between biomarkers of AD and white matter alterations. They found that increased Ttau, Ptau and decreased Aβ42 were associated with decreased MWF and other MRI quantitative measures indicating white matter alterations. These findings reinforce the theory that AD impacts white matter microstructure and suggest that measurements of white matter may be important in identifying early Alzheimer’s. The study was limited by a small sample size that also had a low (19%) percentage of males and a high percentage of individuals genetically predisposed to developing Alzheimer’s. Nonetheless, this study shows that decline in myelin content and other white matter alterations are associated with biomarkers for AD, and the changes in white matter may be a way to identify preclinical Alzheimer’s.


Written By: Wesley Tin, BMSc

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