TY - JOUR
T1 - Effect of APOE genotype on amyloid deposition, brain volume, and memory in cognitively normal older individuals
AU - Lim, Yen Ying
AU - Williamson, Robert
AU - Laws, Simon M.
AU - Villemagne, Victor L.
AU - Bourgeat, Pierrick
AU - Fowler, Christopher
AU - Rainey-Smith, Stephanie
AU - Salvado, Olivier
AU - Martins, Ralph N.
AU - Rowe, Christopher C.
AU - Masters, Colin L.
AU - Maruff, Paul
AU - Chambers, Brian
AU - Chiu, Edmond
AU - Clarnette, Roger
AU - Darby, David
AU - Davison, Mary
AU - Drago, John
AU - Drysdale, Peter
AU - Gilbert, Jacqueline
AU - Lim, Kwang
AU - Lautenschlager, Nicola
AU - LoGiudice, Dina
AU - McCardle, Peter
AU - McFarlane, Steve
AU - Mander, Alastair
AU - Merory, John
AU - O'Connor, Daniel
AU - Scholes, Ron
AU - Samuel, Mathew
AU - Trivedi, Darshan
AU - Woodward, Michael
AU - The AIBL Research Group
PY - 2017/6/23
Y1 - 2017/6/23
N2 - Background: The association between the apolipoprotein E (APOE) ϵ4 allele and high risk of developing Alzheimer's disease (AD) dementia before the age of 80 has been recognized for over 30 years. However, the timing and mode of action of APOE is not understood, nor has there been a detailed analysis of the effect of APOE genotype on memory, hippocampal volume, and amyloid-β (Aβ) levels in cognitively normal adults. Objective: Examine the effect of APOE allelic genotype on the relationship between Aβ levels, hippocampal volume, and memory in cognitively normal adults. Methods: This is a cross-sectional study of 989 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, all of whom underwent APOE genotyping and memory assessment. A subset of this group underwent PET neuroimaging for Aβ (n = 585) and MRI for hippocampal volume (n = 303). Results: APOE ϵ4 homozygotes (ϵ4/ϵ4) showed significantly worse episodic memory and higher Aβ levels than ϵ4 heterozygotes. The relationship between increasing Aβ levels and worse episodic memory was significant for ϵ3 homozygotes (ϵ3/ϵ3), ϵ4 heterozygotes, and strongest for ϵ4 homozygotes. There were no differences in hippocampal volume between APOE groups; the relationship between smaller hippocampal volume and worse episodic memory was significant only for ϵ4 homozygotes. Conclusion: APOE acts in a co-dominant fashion on Aβ levels, episodic memory, and hippocampal volume in cognitively normal older adults. APOE ϵ4 is central to the events that lead to AD in cognitively normal older adults, likely through a quantitative role in the disruption of Aβ clearance.
AB - Background: The association between the apolipoprotein E (APOE) ϵ4 allele and high risk of developing Alzheimer's disease (AD) dementia before the age of 80 has been recognized for over 30 years. However, the timing and mode of action of APOE is not understood, nor has there been a detailed analysis of the effect of APOE genotype on memory, hippocampal volume, and amyloid-β (Aβ) levels in cognitively normal adults. Objective: Examine the effect of APOE allelic genotype on the relationship between Aβ levels, hippocampal volume, and memory in cognitively normal adults. Methods: This is a cross-sectional study of 989 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, all of whom underwent APOE genotyping and memory assessment. A subset of this group underwent PET neuroimaging for Aβ (n = 585) and MRI for hippocampal volume (n = 303). Results: APOE ϵ4 homozygotes (ϵ4/ϵ4) showed significantly worse episodic memory and higher Aβ levels than ϵ4 heterozygotes. The relationship between increasing Aβ levels and worse episodic memory was significant for ϵ3 homozygotes (ϵ3/ϵ3), ϵ4 heterozygotes, and strongest for ϵ4 homozygotes. There were no differences in hippocampal volume between APOE groups; the relationship between smaller hippocampal volume and worse episodic memory was significant only for ϵ4 homozygotes. Conclusion: APOE acts in a co-dominant fashion on Aβ levels, episodic memory, and hippocampal volume in cognitively normal older adults. APOE ϵ4 is central to the events that lead to AD in cognitively normal older adults, likely through a quantitative role in the disruption of Aβ clearance.
KW - Alzheimer's disease
KW - amyloid
KW - apolipoprotein E
KW - hippocampal volume
KW - memory
KW - mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=85021257552&partnerID=8YFLogxK
U2 - 10.3233/JAD-170072
DO - 10.3233/JAD-170072
M3 - Article
C2 - 28550258
AN - SCOPUS:85021257552
SN - 1387-2877
VL - 58
SP - 1293
EP - 1302
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -