Biomarkers in Alzheimer’s disease

In 1984, clinical diagnostic guidelines for probable Alzheimer’s Disease (AD) were created by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. The 1984 criteria have been successfully used for 27 years. In the past decade, molecular biomarkers have been developed. Hence, revised criteria were published in 2011 for the clinical diagnosis of AD, mild cognitive impairment due to AD, and preclinical AD. It is well known that the pathological processes in the CNS of AD patients start more than a decade before the first symptoms of AD are noticed. Due to the advances in research, brain imaging and tests based on cerebrospinal şuid (CSF) biomarkers have been implemented to provide evidence of an ongoing pathophysiological progression of AD and it is also possible to make a pre-dementia diagnosis of AD. Reduced levels of beta-amyloid in the CSF, elevated levels of CSF tau or hyperphosphorylated tau are found in individuals with AD. Extracellular accumulations of amyloid β (Aβ) in senile plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau (P-tau), the total amount of tau (T-tau) which reşects the intensity of neuroaxonal degeneration are revealed as characteristic hallmarks of AD. Both cross-sectional and longitudinal studies have evaluated the association between the core CSF AD biomarkers and preclinical AD. CSF levels of Aβ42 alone or in combination with T-tau or P-tau have been associated with future development of cognitive impairment in cognitively normal individuals at the time of lumbar puncture. Increased T-tau: Aβ42 ratio or low levels of CSF Aβ42 have been found to predict conversion to minimal cognitive impairment in cognitively normal. A large multicenter study found that the combination of Aβ42:P-tau ratio and T-tau predicted a sensitivity of 83% and a specificity of 72% for progression to AD. Hansson et al. found that CSF level of Aβ42, T-tau and P-tau among MVI patients could predict progression to AD after a follow up period of 5.2 years. In differential diagnosis among other dementias, P-tau may have a greater value since it is more AD-specific. T-tau is not AD-specific since increase levels of T-tau are also seen in head trauma, disease or acute stroke. Biomarkers may provide early disease detection and lead to effective early treatment of AD. Apart from the core biomarkers, there are several candidate biomarkers of CSF and blood hat need to be verified in future studies.