Predictive Utility of Plasma Amyloid and Tau for Cognitive Decline in Cognitively Normal Adults

Alzheimer's disease (AD) is the most common neurodegenerative disease affecting mostly elderly adults. Recent diagnostic criteria for AD recommend the use of imaging and/or cerebrospinal fluid (CSF) biomarkers together with clinical presentation for a more persuasive diagnosis. The invasiveness and expense of such examinations have led to the search for blood-based biomarkers. The plasma levels of amyloid-β (Aβ) protein and tau peptides have been found to correlate with CSF levels and imaging findings in patients with AD. This study was conducted to explore the predictive utility of plasma Aβ1-42 and total tau (t-tau) levels for cognitive decline in healthy adults.

In this prospective longitudinal study, we enrolled adults aged ≥ 50 years with normal cognition at Taipei Veterans General Hospital from November 2016 to April 2019. Blood samples were collected on recruitment, and plasma Aβ1-42 and t-tau levels were quantified through immunomagnetic reduction. Thorough neurophysiological assessment was performed at baseline and at the annual follow-up visit. The participants were divided into two groups according to cognitive decline. The predictive utility of Aβ1-42 and t-tau levels was evaluated by receiver operating characteristic curve analysis.

Of 60 participants recruited, seven participants progressed to mild cognitive impairment and 53 retained normal cognition on follow-up (average 1.07 ± 0.2 years). The baseline levels of plasma biomarkers (Aβ1-42, t-tau, and Aβ1-42 × t-tau) were significantly higher in the progressive than in the stable group (p = 0.005, p = 0.007, and p = 0.005, respectively). Higher plasma biomarker levels (Aβ1-42 ≥ 16.96 pg/ml and Aβ1-42 × t-tau ≥ 382 pg2/ml2) predicted more cognitive decline on annual follow-up visits.

Plasma Aβ1-42 and t-tau levels have predictive utility for cognitive decline, even in subjects with normal cognition. Higher baseline plasma Aβ1-42 and t-tau levels may indicate a higher risk of cognitive decline in cognitively normal adults.