Effect of APOE and CD33 on Cognitive Decline.
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2015-01
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Abstract
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An Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ε4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE.Methods
Participants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ε4 alleles and either a high or low g-score: APOE ε4-/low g-score; APOE ε4-/high g-score; APOE ε4+/low g-score; and APOE ε4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE.Results
Individuals in the APOE ε4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ε4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons.Conclusions
Individuals with multiple AD risk genes in addition to having one or more APOE ε4 alleles are at greater risk of cognitive decline than individuals with either APOE ε4 or a high genetic risk score. Among those with one or more APOE ε4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.Type
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Hayden, Kathleen M, Michael W Lutz, Maragatha Kuchibhatla, Cassandra Germain and Brenda L Plassman (2015). Effect of APOE and CD33 on Cognitive Decline. PloS one, 10(6). p. e0130419. 10.1371/journal.pone.0130419 Retrieved from https://hdl.handle.net/10161/33770.
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Scholars@Duke
Michael William Lutz
Developing and using computational biology methods to understand the genetic basis of disease with a focus on Alzheimer’s Disease. Recent work has focused on identification and validation of clinically-relevant biomarkers for Alzheimer’s disease and Alzheimer’s disease with Lewy bodies.
Maragatha Kuchibhatla
Statistical research methodology, analysis of repeated measurements, latent growth curve models, latent class growth models, classification and regression trees,
designing clinical trials, designing clinical trials in psychiatry -- both treatment and non-treatment
trials in various comorbid populations.
Brenda Lee Plassman
My research interests include the following areas:
1) Epidemiological studies to examine the prevalence and incidence of dementia and cognitive impairment, not dementia (CIND)
2) Studies examining risk and protective factors for dementia and CIND
3) Behavioral genetics of aging and dementia with an emphasis on twin studies
4) Long term outcomes of traumatic brain injury
5) Oral health and cognition in later life
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