Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12420
Title: APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease.
Austin 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: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
National Ageing Research Institute, Parkville, VIC, Australia
Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia
CogState Ltd, Melbourne, VIC, Australia
Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia
Co-operative Research Centre for Mental Health.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
Academic Unit for Psychiatry of Old Age, Department of Psychiatry, St. Vincent's Health, University of Melbourne, Kew, VIC, Australia
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia
Department of Neurology, Rhode Island Hospital, Providence, RI, USA
Issue Date: 7-Oct-2014
Publication information: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/12420
DOI: 10.1038/mp.2014.123
URL: https://pubmed.ncbi.nlm.nih.gov/25288138
Type: Journal Article
Appears in Collections:Journal articles

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