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2017 Grants - Lim
Cognitive and Biological Changes in APOE4 Carriers: Implications for Alzheimer’s Disease
Yen Ying Lim, Ph.D.
The Florey Institute of Neuroscience and Mental Health
2017 Alzheimer’s Association Research Grant (AARG)
What are the earliest signs of Alzheimer’s disease in middle-aged adults who carry the APOE-e4 genetic variation?
The apolipoprotein E (APOE) gene codes for the production of ApoE protein, a naturally occurring protein in the brain. There are different versions of the APOE gene, and one of those versions, known as APOE-e4, is a known risk factor for Alzheimer’s disease. Carrying APOE-e4 can hasten the rate of cognitive decline and promote formation of abnormal beta-amyloid “plaques” in the brain, a hallmark of Alzheimer’s disease. Recent studies suggest that Alzheimer’s-associated brain changes can be detected many years prior to the onset of clinical symptoms, but most studies of APOE-e4 carriers have been in people aged 65 years and older. Studying middle-aged individuals who carry APOE-e4 offers the opportunity to detect the earliest signs of Alzheimer’s disease and inform future prevention or treatment strategies.
Yen Ying Lim, Ph.D., and colleagues have planned a study to look for the earliest signs of Alzheimer’s disease in a large group of middle-aged individuals (aged 40-60) who have the APOE-e4 genetic risk factor for Alzheimer’s disease. The study participants are part of the Healthy Brain Project and will include 1,000 people who carry at least one copy of the APOE-e4 gene and 3,000 who carry forms of the APOE gene that do not increase risk (i.e. non-carriers). The participants will be assessed for changes in memory function, mood and lifestyle factors over several years. A subset of the participants will also have cerebrospinal fluid (CSF) collected for measurements of beta-amyloid and abnormal tau. Changes in the levels of abnormal proteins in the CSF have been shown to be effective “biomarkers” for Alzheimer’s disease progression.
These studies could allow us to detect the earliest signs of cognitive decline and biomarker changes in individuals at genetic risk for Alzheimer’s disease. In addition, this study will help determine how lifestyle factors may influence these changes over time. A better understanding of these mechanisms is critical for designing treatment strategies (lifestyle changes and/or drug treatments) that could potentially slow, halt or prevent Alzheimer’s disease.