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Aging and sex impact plasma NFL and t‐Tau trajectories in individuals at risk for Alzheimer’s disease
Author(s) -
Baldacci Filippo,
Lista Simone,
Manca Maria Laura,
Lemercier Pablo,
Chiesa Patrizia Andrea,
Zetterberg Henrik,
Blennow Kaj,
Potier MarieClaude,
Habert MarieOdile,
Cavedo Enrica,
Dubois Bruno,
Vergallo Andrea,
Hampel Harald
Publication year - 2020
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 - 10.1002/alz.041792
Subject(s) - apolipoprotein e , medicine , cohort , dementia , vitamin d and neurology , atrophy , psychology , memory clinic , tau protein , endocrinology , cognitive decline , alzheimer's disease neuroimaging initiative , disease , oncology , gastroenterology , alzheimer's disease
Background Neurofilament light (NFL) chain and total Tau (t‐Tau) proteins are established biomarkers of axonal degeneration. Increased plasma concentrations of both proteins are associated with worsening rate of cognitive performance, cerebral atrophy, and hypometabolism in prodromal and dementia phases of Alzheimer’s disease (AD). Few studies explored, in cognitively healthy individuals, the potential influence of key biological factors – age, sex, Apolipoprotein E ( APOE ) ε4 allele – on NFL and t‐Tau plasma concentrations as well as their association with comorbidities, brain amyloid beta (Aβ) deposition, and cognitive scores. Method The ultrasensitive SiMoA platform was used to measure plasma NFL and t‐Tau concentrations at three time points (baseline: N=316; one‐ and three‐year follow‐up: N=79) in the INSIGHT‐preAD cohort, a large observational monocentric French academic cohort (Pitié‐Salpêtrière University Hospital, Paris) of individuals with subjective memory complaints (SMC), a condition at risk for AD. Result Age affected plasma NFL concentrations ( P <0.001). Sex influenced plasma t‐Tau ( P =0.003), with females showing a higher concentration increase than males, across the three time points. A significant effect of sex*age interaction was also reported ( P =0.038). No effect of APOE ε4 was found on either NFL or t‐Tau. Plasma vitamin B12 deficiency was associated with increased t‐Tau concentrations. Plasma NFL significantly increased at one‐year ( P =0.007) and three‐year ( P <0.001) follow‐up versus baseline. Plasma t‐Tau significantly increased at three‐year follow‐up ( P =0.004) versus baseline. Plasma NFL was associated with plasma t‐Tau ( P =0.011) and cerebrospinal fluid NFL ( P <0.001) concentrations, at baseline. Baseline plasma NFL was associated with increased Aβ deposition rate, at two‐year follow‐up, in the left posterior cingulate ( P =0.019) and the bilateral inferior parietal gyri ( P =0.013). Baseline plasma NFL and the rate of change of plasma t‐Tau were inversely associated with cognitive score ( P =0.029 and P =0.015, respectively). Conclusion Age and female sex affect plasma NFL and t‐Tau longitudinal trajectories, respectively, in SMC individuals. Exploring the impact of biological variables on AD biomarkers is crucial for their clinical validation in blood. Moreover, there is a potential effect of plasma NFL concentrations on brain amyloid plaques deposition.