Validation of biomarkers for dementia and mild cognitive impairment.

Diagnosis of sporadic Alzheimer's disease (AD) is based on clinical exclusion criteria and the required diagnostic work-up is time-consuming and expensive at best resulting in a diagnosis of probable AD. In specialized centers, a diagnostic accuracy of maximally 68% is obtained. Besides, diagnosis is only definite on post-mortem neuropathological examination of the brain. Therefore, validated biological markers allowing diagnosing AD at an early stage of the disease are highly desirable. In AD, several proteins accumulate in the brain. As the cerebrospinal fluid (CSF) is in close contact with the brain, those proteins can be detected in the CSF. Using biomarker-based models, a combined assessment of CSF levels of β-amyloid peptide (Aβ1-42), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) increases discriminatory power allowing differentiating AD from other dementias. As this combined assessment using newly developed biomarker-based models has not been validated and as its discriminatory power and its added diagnostic value remain to be established, we set up a prospective study, including dementia (n=800) and MCI (n=200) patients as well as healthy control subjects (n=200). As Aβ isoforms can be detected in plasma, diagnostic accuracy for (early) AD diagnosis will be tested as well.

Keywords:DEMENTIA, MILD COGNITIVE IMPAIRMENT, BIOLOGICAL MARKERS

Disciplines:Laboratory medicine, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing