Aamira J Huq1, Peter Fransquet2, Simon M Laws3, Joanne Ryan2, Robert Sebra4, Colin L Masters5, Ingrid M Winship6, Paul A James6, Paul Lacaze2. 1. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Genomic Medicine, Royal Melbourne Hospital, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. Electronic address: Aamira.Huq@mh.org.au. 2. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 3. Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia. 4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. The Florey Institute, University of Melbourne, Parkville, Victoria, Australia. 6. Department of Genomic Medicine, Royal Melbourne Hospital, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
Abstract
INTRODUCTION: Individuals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These "resilient" individuals may carry protective genetic factors. METHODS: This study aimed to systematically review any previous studies that involved resilient APOE ε4 homozygotes and to identify possible modifying or protective genetic factors. RESULTS: Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7 rs10553596 and SERPINA3 rs4934-A/A, had strong evidence. DISCUSSION: We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE ε4 homozygotes and heterozygotes together because of small sample sizes and used control populations too young to be clearly defined as controls for LOAD.
INTRODUCTION: Individuals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These "resilient" individuals may carry protective genetic factors. METHODS: This study aimed to systematically review any previous studies that involved resilient APOE ε4 homozygotes and to identify possible modifying or protective genetic factors. RESULTS: Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7rs10553596 and SERPINA3rs4934-A/A, had strong evidence. DISCUSSION: We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE ε4 homozygotes and heterozygotes together because of small sample sizes and used control populations too young to be clearly defined as controls for LOAD.
Authors: Sarah M Neuner; Maria Telpoukhovskaia; Vilas Menon; Kristen M S O'Connell; Timothy J Hohman; Catherine C Kaczorowski Journal: Trends Neurosci Date: 2022-03-17 Impact factor: 16.978
Authors: Aamira J Huq; Brian Fulton-Howard; Moeen Riaz; Simon Laws; Robert Sebra; Joanne Ryan; Alan E Renton; Alison M Goate; Colin L Masters; Elsdon Storey; Raj C Shah; Anne Murray; John McNeil; Ingrid Winship; Paul A James; Paul Lacaze Journal: Alzheimers Dement (Amst) Date: 2021-08-05
Authors: Vijay K Ramanan; Timothy G Lesnick; Scott A Przybelski; Michael G Heckman; David S Knopman; Jonathan Graff-Radford; Val J Lowe; Mary M Machulda; Michelle M Mielke; Clifford R Jack; Ronald C Petersen; Owen A Ross; Prashanthi Vemuri Journal: Acta Neuropathol Commun Date: 2021-03-23 Impact factor: 7.578
Authors: Lindsey Rubin; Lucy A Ingram; Nicholas V Resciniti; Brianna Ashford-Carroll; Katherine Henrietta Leith; Aubrey Rose; Stephanie Ureña; Quentin McCollum; Daniela B Friedman Journal: Front Public Health Date: 2021-12-24
Authors: Moeen Riaz; Aamira Huq; Joanne Ryan; Suzanne G Orchard; Jane Tiller; Jessica Lockery; Robyn L Woods; Rory Wolfe; Alan E Renton; Alison M Goate; Robert Sebra; Eric Schadt; Amy Brodtmann; Raj C Shah; Elsdon Storey; Anne M Murray; John J McNeil; Paul Lacaze Journal: Aging Cell Date: 2021-05-26 Impact factor: 9.304