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P4‐280: BRAIN AMYLOID BURDEN, SLEEP, AND CIRCADIAN REST/ACTIVITY RHYTHMS: SCREENING FINDINGS FROM A4 AND LEARN
Author(s) -
Rosenberg Paul B.,
Zipunnikov Vadim,
Lu Zeyun,
Raman Rema,
Carlsson Cynthia M.,
Mintzer Jacobo E.,
Marshall Gad A.,
Porsteinsson Anton P.,
Yaari Roy,
Wanigatunga Sarah K.,
Romano Caitlin,
Wu Mark N.,
Aisen Paul S.,
Sperling Reisa A.,
Spira Adam P.
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.2018.07.102
Subject(s) - circadian rhythm , actigraphy , audiology , medicine , alzheimer's disease , sleep (system call) , psychology , endocrinology , disease , computer science , operating system
3-8 year period were measured via multiple reaction monitoring (MRM) mass spectrometry. CSF Ab1-42, total-Tau (tTau) and phosphorylated-Tau (pTau-181) were measured using Luminex xMAP platform, and brain hippocampal volume was obtained from magnetic resonance imaging (MRI). From these candidate markers, optimal diagnostic signatures with decision thresholds on a few markers that separate AD and normal subjects were first identified via unbiased regression and tree-based algorithms (Huang et al, 2017). The best performing signature determined via cross-validation was then tested in an independent group of MCI subjects to predict their future progression to AD. This procedure was first carried out on only four well-known markers (CSF Ab1-42, tTau and pTau, and MRI hippocampal volume), then using 320 MRM peptides, and finally using all the markers. Results:This multivariate analysis yielded a simple diagnostic signature comprising CSF tTau to Ab1-42 ratio, MRI hippocampal volume and a novel VGF peptide, with a decision threshold on each marker. When tested in an independent MCI group, signature positive subjects progress 4-fold faster to AD with 81% positive predictive value (PPV). However, with only the well-known markers (i.e., without the VGF peptide), this drops to 2-fold faster progression to AD with 65% PPV. VGF is a neurosecretory protein that may be a marker for neuronal dysfunction. Conclusions:This 4-marker signature is a major advance over the current diagnostics based on widely used markers (Shaw et al., 2009), and is much easier to use in practice than recently published complex signatures (Llano et al., 2017, Spellman et al., 2015). In addition, this signature reinforces the ATN construct from the 2018 NIA-AA research framework.