Cerebrospinal fluid A beta 42 is the best predictor of clinical progression in patients with subjective complaints

Background: The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid beta(1-42) (A beta 42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints. Methods: We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF A beta 42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini-Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD. Results: We included 127 patients with subjective complaints (age 60 +/- 10 years, 61 [48%] females, MMSE 29 +/- 1). At baseline, A beta 42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). A beta 42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8-66.4). The adjusted BR associated with tau was 2.8 (0.9-9.2) and with ptau 2.6 (0.8-8.2). Combinations of biomarkers had a lower predictive value than A beta 42 alone. Conclusion: Low A beta 42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of A beta 42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.