title: Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals.
abstract: The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.
authors.affiliation: CEDAR, Center for Demographic and Aging Research, Umeå University, S-901 87 Umeå, Sweden; UFBI, Umeå centre for Functional Brain Imaging, Umeå University, Sweden. Electronic address: cj.boraxbekk@umu.se.
authors.forename: C J
authors.initials: CJ
authors.lastname: Boraxbekk
authors.affiliation: National Ageing Research Institute, Parkville, Victoria, Australia; Department of Psychiatry, University of Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kochan
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lee
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Mathematics and Statistics, Murdoch University, WA, Australia.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, UNSW, Sydney, NSW, Australia.
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, UNSW, Sydney, NSW, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Department of Developmental Disability Neuropsychiatry, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Reppermund
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Department of Developmental Disability Neuropsychiatry, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Dementia Collaborative Research Centre, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Centre for Healthy Brain Ageing, UNSW Australia, Sydney, NSW, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.affiliation: National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology / Q000523:psychology; D001284:Atrophy / Q000235:genetics; D001315:Australia / Q000453:epidemiology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008569:Memory Disorders / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D061212:Memory, Episodic; D009483:Neuropsychological Tests; D009929:Organ Size; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C472551:CLSTN2 protein, human; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C513637:WWC1 protein, human
keywords: CLSTN2; Episodic memory; Gene–gene interactions; Hippocampus; KIBRA