The influence of Apolipoprotein E genotype on regional pathology in Alzheimer's disease

Persistent Link:
http://hdl.handle.net/10150/610066
Title:
The influence of Apolipoprotein E genotype on regional pathology in Alzheimer's disease
Author:
Sabbagh, Marwan; Malek-Ahmadi, Michael; Dugger, Brittany; Lee, Katarina; Sue, Lucia; Serrano, Geidy; Walker, Douglas; Davis, Kathryn; Jacobson, Sandra; Beach, Thomas
Affiliation:
The Cleo Robert Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA; Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, AZ, USA
Issue Date:
2013
Publisher:
BioMed Central
Citation:
Sabbagh et al. BMC Neurology 2013, 13:44 http://www.biomedcentral.com/1471-2377/13/44
Journal:
BMC Neurology
Rights:
© 2013 Sabbagh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:Carriers of the ApoE 4 allele are at a greater risk for developing Alzheimer's disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among 4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency.METHODS:566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE 4 carriers and 254 ApoE 4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (4 carrier vs. 4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal).RESULTS:4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than 4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE 4 carrier status, 4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, 4 carriers tended to have significantly more "frequent" scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older.CONCLUSIONS:ApoE 4 carriers had a significantly higher percentage of "frequent" scores for plaques and tangles when compared to ApoE 4 non-carriers for several brain regions. However, 4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.
EISSN:
1471-2377
DOI:
10.1186/1471-2377-13-44
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2377/13/44

Full metadata record

DC FieldValue Language
dc.contributor.authorSabbagh, Marwanen
dc.contributor.authorMalek-Ahmadi, Michaelen
dc.contributor.authorDugger, Brittanyen
dc.contributor.authorLee, Katarinaen
dc.contributor.authorSue, Luciaen
dc.contributor.authorSerrano, Geidyen
dc.contributor.authorWalker, Douglasen
dc.contributor.authorDavis, Kathrynen
dc.contributor.authorJacobson, Sandraen
dc.contributor.authorBeach, Thomasen
dc.date.accessioned2016-05-20T08:57:48Z-
dc.date.available2016-05-20T08:57:48Z-
dc.date.issued2013en
dc.identifier.citationSabbagh et al. BMC Neurology 2013, 13:44 http://www.biomedcentral.com/1471-2377/13/44en
dc.identifier.doi10.1186/1471-2377-13-44en
dc.identifier.urihttp://hdl.handle.net/10150/610066-
dc.description.abstractBACKGROUND:Carriers of the ApoE 4 allele are at a greater risk for developing Alzheimer's disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among 4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency.METHODS:566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE 4 carriers and 254 ApoE 4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (4 carrier vs. 4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal).RESULTS:4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than 4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE 4 carrier status, 4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, 4 carriers tended to have significantly more "frequent" scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older.CONCLUSIONS:ApoE 4 carriers had a significantly higher percentage of "frequent" scores for plaques and tangles when compared to ApoE 4 non-carriers for several brain regions. However, 4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2377/13/44en
dc.rights© 2013 Sabbagh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleThe influence of Apolipoprotein E genotype on regional pathology in Alzheimer's diseaseen
dc.typeArticleen
dc.identifier.eissn1471-2377en
dc.contributor.departmentThe Cleo Robert Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USAen
dc.contributor.departmentCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USAen
dc.contributor.departmentLaboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, AZ, USAen
dc.identifier.journalBMC Neurologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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