@article{6c78b496a8da4aca8c5523909b1f6714,
title = "Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults",
abstract = "Biomarkers associated with Alzheimer's disease (AD)-like brain atrophy in healthy individuals may identify mechanisms involved in early stage AD. Aside from cerebrospinal fluid (CSF) β-amyloid42 (Aβ42) and tau, no studies have tested associations between CSF proteins and AD-like brain atrophy. We studied 90 healthy elders, who underwent lumbar puncture at baseline, and serial magnetic resonance imaging scans for up to 4 years. We tested statistical effects of baseline CSF proteins (N= 70 proteins related to Aβ42-metabolism, microglial activity, and synaptic/neuronal function) on atrophy rates in 7 AD-related regions. Besides the effects of Aβ42 and phosphorylated tau (P-tau) that were seen in several regions, novel CSF proteins were found to have effects in inferior and middle temporal cortex (including apolipoprotein CIII, apolipoprotein D, and apolipoprotein H). Several proteins (including S100β and matrix metalloproteinase-3) had effects that depended on the presence of brain Aβ pathology, as measured by CSF Aβ42. Other proteins (including P-tau and apolipoprotein D) had effects even after adjusting for CSF Aβ42. The statistical effects in this exploratory study were mild and not significant after correction for multiple comparisons, but some of the identified proteins may be associated with brain atrophy in healthy persons. Proteins interacting with CSF Aβ42 may be related to Aβ brain pathology, whereas proteins associated with atrophy even after adjusting for CSF Aβ42 may be related to Aβ-independent mechanisms.",
keywords = "Alzheimer's disease, Atrophy, Biomarkers, Cerebrospinal fluid, Longitudinal",
author = "Niklas Mattsson and Philip Insel and Rachel Nosheny and Trojanowski, {John Q.} and Shaw, {Leslie M.} and Jack, {Clifford R.} and Duygu Tosun and Michael Weiner",
note = "Funding Information: N.M., P.I., R.N., and D.T. report no conflicts of interest. L.M.S. previously was a consultant for Innogenetics, and collaborates on quality assessment activities as part of the Alzheimer's Disease Neuroimaging Initiative; serves as a consultant to Janssen AI R & D on biomarker studies. J.Q.T. may accrue revenue in the future on patents submitted by the University of Pennsylvania wherein he is co-Inventor; he received revenue from the sale of Avid to Eli Lily as co-inventor on imaging related patents submitted by the University of Pennsylvania, and is the William Maul Measey-Truman G. Schnabel, Jr, M.D. Professor of Geriatric Medicine and Gerontology. M.W. has been on scientific advisory boards for Pfizer and BOLT Inter-national; has been a consultant for Pfizer Inc, Janssen, KLJ Associates, Easton Associates, Harvard University, inThought, INC Research, Inc, University of California, Los Angeles, Alzheimer's Drug Discovery Foundation and Sanofi-Aventis Groupe; has received funding for travel from Pfizer, AD PD meeting, Paul Sabatier University, Novartis, Tohoku University, MCI Group, France, Travel eDreams, Inc, Neuroscience School of Advanced Studies (NSAS), Danone Trading, BV, CTAD ANT Congres; serves as an associate editor of Alzheimer's & Dementia; has received honoraria from Pfizer, Tohoku University, and Danone Trading, BV; has research support from Merck, Avid, DOD and VA; and has stock options in Synarc and Elan. C.R.J. provides consulting services for Siemens Healthcare and Janssen Research and Development L.L.C. He receives research funding from the National Institutes of Health (R01-AG011378, RO1-AG041851, RO1-AG037551, U01-HL096917, U01-AG032438, U01-AG024904), and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. ",
year = "2014",
month = mar,
doi = "10.1016/j.neurobiolaging.2013.08.027",
language = "English (US)",
volume = "35",
pages = "614--622",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "3",
}