Biomarkers may help predict risk of Alzheimer’s disease

Several cerebrospinal fluid (CSF) biomarkers showed good accuracy in identifying patients with mild cognitive impairment who progressed to Alzheimer’s disease, revealed by US researchers in JAMA.

Alzheimer disease (AD) is the most common cause of dementia, affecting more than 15 million individuals worldwide. Because of the type of progression of the disease, there is a need for methods enabling early diagnosis.

“Treatments would need to be initiated very early in the disease process, before the neurodegenerative process is too severe. Much focus has thus been directed on patients with mild cognitive impairment (MCI), which is a syndrome characterized by cognitive impairment beyond the age-adjusted norm, but not severe enough to fulfill the criteria for dementia,” the authors write.

Biochemical changes in the brain are reflected in the CSF, and intense research efforts have been made to develop biomarkers for the central pathogenic processes in Alzheimer’s disease (AD) that can be used as diagnostic tools.

Niklas Mattsson, M.D., of the Sahlgrenska Academy at the University of Gothenburg, M?lndal, Sweden, and colleagues conducted a multicenter study to assess the diagnostic accuracy of the CSF biomarkers ?-amyloid1-42 (A?42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) in identifying incipient AD in a large group of patients with MCI.

“We determined in a large multicenter study that the CSF biomarkers A?42, T-tau, and P-tau can be used to predict with good accuracy which MCI patients will develop AD, as previously found in smaller studies. This multicenter collaboration avoids several of the risks of biases associated with single-center studies by having included substantially more patients than previous studies. Cerebrospinal fluid biomarker changes were found to be significantly associated with incipient AD. However, the considerable intercenter variations in assays and patient assessments described point to a need for standardization of sample handling as well as of clinical assessments. Although each memory clinic center followed up its cohorts prospectively and used established clinical criteria, a limitation of the present study is the lack of fully harmonized study protocols for all centers, which might account for some of the intercenter variations that we observed,” the researchers write.

Using CSF A?42, T-tau, and P-tau in memory clinics will result in some false-positive cases, as well as false-negative cases, and the biomarkers may therefore be useful primarily as screening tools, selecting individuals for a detailed further clinical follow-up.

Source: Journal of the American Medical Association, USA



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