Nutrition, brain health and Alzheimer’s disease risk in females

MINIHANE_U22DTP

Dementia, of which Alzheimer’s Disease (AD) is the main form, currently affects 50 million people worldwide and this is set to triple by 2050. Two thirds of AD patients are female. Work generated by our group over the last five years has indicated that this is partly due to a greater physiological impact of the ‘risky’ APOE4 genotype (25% UK population) on age-related cognitive decline in females along with a significant loss of cognitive function associated with the menopausal transition. We have additionally shown that in females, ageing, having an APOE4 genotype, and being post-menopausal is associated with a loss of neuronal synaptic function, neuroinflammation and lower levels of the omega-3 fatty acid, DHA, in the brain.

The PhD will use data from the UK BIOBANK cohort (n=260,000 females), animal models, and a range of laboratory (e.g. GC-FID for brain and blood fatty acid analysis) and molecular biology techniques, to investigate the independent and interactive impact of APOE genotype, DHA intake and status, menopause and estrogen replacement therapy on neurophysiology and cognition.

The research will contribute to the identification of effective strategies to promote brain health in older ages in women. In addition, the student will be provided with training in scientific writing, presentation, data management, communication and entrepreneurship skills, encouraged to attend and present at national and international conferences, and undertake a three-month placement.

This project will suit applicants with a primary or MSc degree in nutrition, biochemistry, neurosciences or a related biological science.

References

Pontifex MG, Martinsen A, Saleh RNM, Harden G, Tejera N, Müller M, Fox C, Vauzour D, Minihane AM. APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE-TR mice. FASEB J. 2021;35(5):e21583.

Schulze MB, Minihane AM, Saleh RNM, Risérus U. Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases. Lancet Diabetes Endocrinol. 2020;8(11):915-30.

Martinsen A, Tejera N, Vauzour D, Harden G, Dick J, Shinde S, Barden A, Mori TA, Minihane AM. Altered SPMs and age-associated decrease in brain DHA in APOE4 female mice. FASEB J. 2019;33(9):10315-26.