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O5‐05‐05: UNDULATIONS OF THE PLASMA PROTEOME DEFINE DISTINCT STAGES OF HUMAN LIFESPAN AND REVEAL ACCELERATED AGING IN ALZHEIMER'S DISEASE
Author(s) -
Lehallier Benoit,
Gate David,
Schaum Nicholas,
Nanasi Tibor,
Lee Song Eun,
Yousef Hanadie,
Berdnik Daniela,
Franceschi Claudio,
Wyss-Coray Tony
Publication year - 2019
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.2019.06.4862
Subject(s) - proteome , disease , biology , blood proteins , parabiosis , biological age , bioinformatics , medicine , evolutionary biology , endocrinology
model with Hamiltonian Markov Chain Monte Carlo. NfL elevation onset in the mutation carrier group was defined by the initial age at which 99% credible intervals in the carrier and non-carrier groups did not overlap. Linear mixed effect (LME) models were used to estimate the fixed slope and intercept of mutation carriers and non-carriers. Results: At baseline, NfL was elevated in impaired carriers (mean, 59.9 pg/mL) and unimpaired carriers (mean, 15.8 pg/mL), compared to noncarriers (mean, 8.1 pg/mL) (P < .001). Carriers showed higher NfL levels at average age 38 (7 years before the kindred’s mean age at MCI onset). Longitudinally, LME models estimated that the NfL levels separate the carriers from non-carriers at the age of 28 years (about 17 years before estimated age of clinical onset). Significant associations between plasma NfL levels and agewere observed in carriers and noncarriers (carriers: r1⁄4.32, P<.001; noncarriers (r1⁄4.26, P<.001). Elevated plasma NfL concentrations were associated with lower Mini-Mental-State-Examination (MMSE) and lower episodic memory scores in impaired and unimpaired carriers (e.g. unimpaired: MMSE r1⁄4 -.37; CERAD Word List Recall, r1⁄4-.23, P<. 001), after adjustment for older age. Conclusions: Plasma NfL concentration was significantly elevated in PSEN1 mutation carriers, years before their estimated age of clinical onset. Higher NfL levels were associated with older age, and with lower scores in clinical and cognitive measures. Plasma NfL may be a useful non-invasive biomarker to monitor neurodegeneration in ADAD.