Early detection is vital in the quest to develop a cure for Alzheimer’s disease (AD), and CSF biomarkers (Aβ42, t-tau, p-tau) and MRI morphometry distinguish AD from healthy controls. Aβ42 and neurodegenerative biomarkers may precede clinical symptoms, but it is not clear whether AD invariably follows and whether neuropsychological tests are as sensitive. Aβ42 is related to plaque burden, which was assumed to be the main cause of AD. Evidence is now pointing to other forms of Aβ, for example, soluble Aβ oligomers, and it is possible that plaques are secondary rather than causative to neuronal damage. This makes it less obvious that CSF Aβ42 necessarily is the most potent marker. Atrophy has been regarded as a downstream event, but novel MRI analysis techniques detect atrophy at a stage where the cognitive reductions are small and possibly reversible, and MRI is superior to CSF biomarkers in the prediction of cognitive decline. The impact of biomarkers may be dynamic; changed Aβ42 is seen in cognitively normal, while atrophy causes decrements later. In conclusion, CSF and MRI biomarkers are extremely important, but it is not known whether they can distinguish events that will lead to AD from events that will not before cognitive reductions are measurable.
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