Abstract
Objective: We investigated whether plasma tau was related to preclinical Alzheimer’s disease and predictive of future dementia in participants from the community-based Framingham Heart Study.
Background: The identification of preclinical Alzheimer’s disease and prediction of clinical dementia are limited by the invasive and cost prohibitive nature of current biomarkers. The discovery of minimally invasive and costeffective blood-based biomarkers for Alzheimer’s disease has the potential to transform clinical research and practice by permitting widespread low-cost screening, risk stratification, and efficient identification of at-risk subjects for inclusion in early Alzheimer’s disease dementia prevention trials.
Design/Methods: Total tau was measured from plasma using a highly sensitive assay and related to the risk of incident dementia over 12 years follow-up (N = 1973, mean age 71±8 years, 45% male). Plasma tau was also related cross-sectionally to cognitive function (N=3832) and hippocampal volume on MRI (N=3238).
Results: We observed 119 cases of incident dementia during follow-up, 93 of which were due to Alzheimer’s disease dementia. Higher plasma tau levels were associated with an increased risk of incident dementia, poorer cognitive function across multiple domains and smaller hippocampal volumes. After adjustments for age and sex, each unit increase in log-transformed plasma tau levels predicted a 148% increase in the risk of Alzheimer’s disease dementia (Hazard ratio, 2.48; 95% confidence interval [CI], 1.32 to 4.65). The addition of plasma tau to a model including age, sex, and APOE ɛ4 allele status yielded a net reclassification improvement of 0.15 (95% CI, 0.01 to 0.40) for 10-year dementia risk categories of low (<10%), intermediate (10–30%), and high (>30%).
Conclusions: Plasma tau corresponded to the preclinical correlates of Alzheimer’s disease and was a strong independent predictor of future dementia. Plasma tau may provide a low-cost, minimally invasive biomarker of Alzheimer’s disease pathophysiology that improves risk stratification for clinical dementia.
Study Supported by: Dr. Pase is funded by an Australian National Health and Medical Research Council Early Career Fellowship (APP1089698). The Framingham Heart Study is supported by the National Heart, Lung and Blood Institute (contracts N01-HC-25195 and HHSN268201500001I), the National Institute of Neurological Disorders and Stroke (NS017950, UH2 NS100605) and the National Institute on Aging (AG033193, AG033040, AG049505, AG049607, AG054076). Prof DeCarli directs the UC Davis Alzheimer’s Disease Center with funding from the NIH (P30 AG010182).
Disclosure: Dr. Pase has nothing to disclose. Dr. Beiser has nothing to disclose. Dr. Himali has nothing to disclose. Dr. Satizabal has nothing to disclose. Dr. Aparicio has nothing to disclose. Dr. DeCarli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis Pharmaceuticals. Dr. Seshadri has nothing to disclose.
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