@article{1b78fa8d4caa4fcca576144527dc5120,
title = "CSF Apo-E levels associate with cognitive decline and MRI changes",
abstract = "Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.",
keywords = "APOE, Alzheimer's disease, Beta amyloid, Cerebrospinal fluid, Dementia, MRI, Neurodegeneration, Plasma, Tau",
author = "Toledo, {Jon B.} and Xiao Da and Weiner, {Michael W.} and Wolk, {David A.} and Xie, {Sharon X.} and Arnold, {Steven E.} and Christos Davatzikos and Shaw, {Leslie M.} and Trojanowski, {John Q.}",
note = "Funding Information: Conflict of interest Dr. Arnold reports grants from NIH, the American Health Assistance Foundation and the Marian S Ware Alzheimer{\textquoteright}s Programseveral pharmaceutical companies, other from Universities, pharmaceutical companies and advisory/speaking honoraria from Universities, pharmaceutical companies and law firms. Dr. Trojanow-ski reports grants from NIH, Bristol Myer Squib, Astra Zeneca and several non-profits, outside the submitted work; In addition, Dr. Tro-janowski has a patent Modified avidin–biotin technique, Method of stabilizing microtubules to treat Alzheimer{\textquoteright}s disease, Method of detecting abnormally phosphorylated tau, Method of screening for Alzheimer{\textquoteright}s disease or disease associated with the accumulation of paired helical filaments, Compositions and methods for producing and using homogeneous neuronal cell transplants, rat comprising straight filaments in its brain, Compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries, Diagnostic methods for Alzheimer{\textquoteright}s disease by detection of multiple MrNAs, Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases, Compositions and methods for producing and using homogenous neuronal cell transplants, Method of identifying, diagnosing and treating alpha-synuclein positive neurodegenerative disorders, Mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype, Microtubule stabilizing therapies for neurodegenerative disorders, and Treatment of Alzheimer{\textquoteright}s and related diseases with an",
year = "2014",
month = may,
doi = "10.1007/s00401-013-1236-0",
language = "English (US)",
volume = "127",
pages = "621--632",
journal = "Acta neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "5",
}