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O3‐09‐05: PLASMA TAU AND NEUROFILAMENT LIGHT CHAIN AS A PROGNOSTIC BIOMARKER OF DISEASE PROGRESSION IN EARLY ALZHEIMER'S DISEASE
Author(s) -
Soares Holly,
Feng Sheng,
Florian Hana,
Gold Michael,
Lon Hoi-Kei,
Mendonca Nuno,
Rendenbach-Mueller Beatrice,
Budur Kumar
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2823
Subject(s) - biomarker , medicine , context (archaeology) , disease , alzheimer's disease neuroimaging initiative , oncology , neuroimaging , cognitive decline , cohort , alzheimer's disease , amyloid (mycology) , cerebrospinal fluid , receiver operating characteristic , pathology , dementia , psychiatry , biology , paleontology , biochemistry
in 1090 persons from two subsamples of the Rotterdam Study using EUROIMMUN assays. Brain volumes (gray matter, white matter and hippocampus) were computed on brain MRI (1.5T). Dementia and its subtypes were defined based on internationally accepted criteria. In each subsample, the association of Ab1 levels with brain volumes was performed using regression models. Association between Ab1 levels and risk of dementia and its subtypes were assessed using Cox-proportional hazard models adjusted for age, sex, education and cardiovascular risk factors. We also investigated the association between plasma Ab1 and dementia among carriers and non-carriers of the APOE-ε4 allele. Results:The mean age of the participants in the two subsamples were 67.8 and 59.1 years. At baseline, higher levels of Ab1-38 was associated with smaller white matter volume (mean difference:-0.04, 95%Confidence Interval (CI):-0.08; -0.00, p1⁄40.04). Higher Ab1-38, Ab1-40 and Ab1-42 levels were associated with reduced risk of dementia specifically AD (adjusted hazards ratios (HR) for Ab1-38: 0.68, 95% CI:0.52-0.90), (HR for Ab1-40: 0.76, 95%CI: 0.58-0.98) and (HR for Ab1-42: 0.69, 95%CI: 0.54-0.89). The association of Ab1-38 and Ab1-42 with dementia persisted after controlling for all isoforms. A significant association was observed for Ab1-38 and Ab1-40 with reduced risk of dementia among APOE-ε4 carriers (HR for Ab1-38: 0.60, 95%CI: 0.42-0.87) and (HR for Ab1-40: 0.64, 95%CI: 0.46-0.98) whereas for Ab1-42, this association was only observed among APOE-ε4 non-carriers. Conclusions: Elevated plasma Ab1-38 and Ab1-42 levels are associated with reduced risk of dementia. Moreover, higher plasma Ab1-38 levels are related to white matter atrophy. These results suggest that plasma Ab1-38 and Ab1-42 are useful biomarkers for identification of individuals at risk of dementia.