Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12420
Title: APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease.
Authors: Lim, Yen Ying;Villemagne, Victor L;Laws, Simon M;Pietrzak, R H;Snyder, P J;Ames, David;Ellis, Kathryn A;Harrington, Karra;Rembach, Alan;Martins, Ralph N;Rowe, Christopher C;Masters, Colin L;Maruff, Paul
Affiliation: 1] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia [2] Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA [3] Department of Neurology, Rhode Island Hospital, Providence, RI, USA.
1] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia [2] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia [3] Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia.
1] Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia [2] Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia [3] Co-operative Research Centre for Mental Health.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
1] Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA [2] Department of Neurology, Rhode Island Hospital, Providence, RI, USA.
1] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, St. Vincent's Health, University of Melbourne, Kew, VIC, Australia [2] National Ageing Research Institute, Parkville, VIC, Australia.
1] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia [2] National Ageing Research Institute, Parkville, VIC, Australia.
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia.
1] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia [2] Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
1] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia [2] CogState Ltd, Melbourne, VIC, Australia.
Issue Date: 7-Oct-2014
Citation: Molecular Psychiatry 2014; 20(11): 1322-8
Abstract: Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4(+)], ɛ4 non-carrier[ɛ4(-)]) and brain-derived neurotrophic factor (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ(-) or Aβ(+). Relative to Aβ(-)ɛ4(-), Aβ(+)ɛ4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aβ(+)ɛ4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ(-)ɛ4(-) and Aβ(-)ɛ4(+) groups. Among Aβ(+) individuals, ɛ4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ(+)ɛ4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ(+)ɛ4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ(-) and Aβ(+) ɛ4(-) groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.Molecular Psychiatry advance online publication, 7 October 2014; doi:10.1038/mp.2014.123.
Internal ID Number: 25288138
URI: http://ahro.austin.org.au/austinjspui/handle/1/12420
DOI: 10.1038/mp.2014.123
URL: http://www.ncbi.nlm.nih.gov/pubmed/25288138
Type: Journal Article
Appears in Collections:Journal articles

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