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Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls.
Acta Neuropathol 2014; 127(5):633-43AN

Abstract

The apolipoprotein E (ApoE) ε4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE ε2, ε3, ε4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE ε4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and Aβ1-42 of which the latter association was weaker and only present in APOE ε4 carriers indicating a differential involvement of ApoE in tau versus Aβ-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE ɛ4 carriers and whether this decrease in plasma ApoE predisposes APOE ɛ4 carriers to AD.

Authors+Show Affiliations

Lunenfeld-Tanenbaum Research Institute, Joseph and Wolf Lebovic Health Centre, Mount Sinai Hospital, Toronto, ON, Canada, edumartinezmorillo@gmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24633805

Citation

Martínez-Morillo, Eduardo, et al. "Total Apolipoprotein E Levels and Specific Isoform Composition in Cerebrospinal Fluid and Plasma From Alzheimer's Disease Patients and Controls." Acta Neuropathologica, vol. 127, no. 5, 2014, pp. 633-43.
Martínez-Morillo E, Hansson O, Atagi Y, et al. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathol. 2014;127(5):633-43.
Martínez-Morillo, E., Hansson, O., Atagi, Y., Bu, G., Minthon, L., Diamandis, E. P., & Nielsen, H. M. (2014). Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathologica, 127(5), pp. 633-43. doi:10.1007/s00401-014-1266-2.
Martínez-Morillo E, et al. Total Apolipoprotein E Levels and Specific Isoform Composition in Cerebrospinal Fluid and Plasma From Alzheimer's Disease Patients and Controls. Acta Neuropathol. 2014;127(5):633-43. PubMed PMID: 24633805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. AU - Martínez-Morillo,Eduardo, AU - Hansson,Oskar, AU - Atagi,Yuka, AU - Bu,Guojun, AU - Minthon,Lennart, AU - Diamandis,Eleftherios P, AU - Nielsen,Henrietta M, Y1 - 2014/03/15/ PY - 2014/01/28/received PY - 2014/03/04/accepted PY - 2014/03/03/revised PY - 2014/3/18/entrez PY - 2014/3/19/pubmed PY - 2014/12/15/medline SP - 633 EP - 43 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 127 IS - 5 N2 - The apolipoprotein E (ApoE) ε4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE ε2, ε3, ε4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE ε4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and Aβ1-42 of which the latter association was weaker and only present in APOE ε4 carriers indicating a differential involvement of ApoE in tau versus Aβ-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE ɛ4 carriers and whether this decrease in plasma ApoE predisposes APOE ɛ4 carriers to AD. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/24633805/Total_apolipoprotein_E_levels_and_specific_isoform_composition_in_cerebrospinal_fluid_and_plasma_from_Alzheimer's_disease_patients_and_controls_ L2 - https://dx.doi.org/10.1007/s00401-014-1266-2 DB - PRIME DP - Unbound Medicine ER -