A Common Variant in the MC1R Gene (p.V92M) is associated with Alzheimer's Disease Risk.
Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer’s disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Aβ1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Aβ1-42/Aβ1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Aβ1-42/Aβ1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Aβ1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Aβ1-42/Aβ1-38. The ratio Aβ1-42/Aβ1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker.