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Effect of APOE and CD33 on Cognitive Decline.

Hayden KM, Lutz MW, Kuchibhatla M, Germain C, Plassman BL - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America; Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina, United States of America.

ABSTRACT

Objective: 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.

No MeSH data available.


Related in: MedlinePlus

Sample Selection Flowchart.Abbreviations: f/up: follow-up; TICS-m: Telephone Interview for Cognitive Status-modified; G-score: genetic risk score.
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pone.0130419.g001: Sample Selection Flowchart.Abbreviations: f/up: follow-up; TICS-m: Telephone Interview for Cognitive Status-modified; G-score: genetic risk score.

Mentions: A total of 8,709 individuals who contributed DNA and cognitive assessments after age 65 were identified from a total of 12,507 participants who provided DNA for genetic analysis (Fig 1). 7,451 of these self-identified as White and had complete data for this analysis. Demographic characteristics of the sample by genetic risk group are shown in Table 1.


Effect of APOE and CD33 on Cognitive Decline.

Hayden KM, Lutz MW, Kuchibhatla M, Germain C, Plassman BL - PLoS ONE (2015)

Sample Selection Flowchart.Abbreviations: f/up: follow-up; TICS-m: Telephone Interview for Cognitive Status-modified; G-score: genetic risk score.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4478019&req=5

pone.0130419.g001: Sample Selection Flowchart.Abbreviations: f/up: follow-up; TICS-m: Telephone Interview for Cognitive Status-modified; G-score: genetic risk score.
Mentions: A total of 8,709 individuals who contributed DNA and cognitive assessments after age 65 were identified from a total of 12,507 participants who provided DNA for genetic analysis (Fig 1). 7,451 of these self-identified as White and had complete data for this analysis. Demographic characteristics of the sample by genetic risk group are shown in Table 1.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America; Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina, United States of America.

ABSTRACT

Objective: 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.

No MeSH data available.


Related in: MedlinePlus