CSF Aß1-42, but not p-Tau181, Predicted Progression from Amnestic MCI to Alzheimer's Disease Dementia.

The purpose of the study was to determine whether Aß1-42 and p-Tau181 cerebral spinal fluid (CSF) levels can predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (ADD) in a 3-year follow-up study. All participants were evaluated blindly by a behavioral neurologist and a neuropsychologist, and classified according to the Petersen criteria for aMCI and according to the Clinical Dementia Rating (CDR) scale. Individuals were also submitted to lumbar puncture at baseline. Levels of Aß1-42 and p-Tau181 were measured by immunoenzymatic assay. Values were adjusted for age and sex. Thirty-one of 33 (93.9%) participants completed follow-up. Approximately 39% of aMCI individuals progressed to ADD. The relative risk of developing ADD in those with Aß1-42 CSF levels lower than 618.5 pg/mL was 17.4 times higher than in those whose levels were higher than 618.5 pg/mL (P = 0.003). p-Tau181 alone did not predict progression to ADD (P = 0.101). The relative risk in those with a p-Tau181/Aß1-42 ratio higher than 0.135 was 5.7 times greater (P < 0.001). Aß1-42 and p-Tau181 explained 40.1% of the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (ΔCERADs) variance (P = 0.008). Aß1-42 strongly predicted progression from aMCI to ADD. p-Tau181 alone, or its relation to Aß1-42, was inferior than Aß1-42 alone as a predictor of progression to ADD.

CSF Aß1-42, but not p-Tau181, differentiates aMCI from SCI.

AIM: Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimer's disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aß1-42) and neurodegeneration (p-Tau181) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. METHODS: We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aß1-42 and p-Tau181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (VM-CERAD). RESULTS: CSF concentration of Aß1-42 was significantly lower (p: .007) and p-Tau181/Aß1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aß1-42 and p-Tau181 (R2: 0.177; ß: -4.43; p: .017). ROC AUC of CSF Aß1-42 was 0.768 and of the p-Tau181/Aß1-42 ratio equals 0.742. Individuals with Aß1-42 < 823 pg/mL levels were 6.0 times more likely to be diagnosed with aMCI (p: .019), with a 68.9% accuracy. Those with p-Tau181/Aß1-42 ratio > 0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CONCLUSION: CSF Aß1-42, but not p-Tau181, level was significantly associated with aMCI.