Sex and Gender in Alzeheimer's Disease

Male vs. Female
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Alzheimer's Disease (AD) is a form of dementia that currently affects 5.4 million people in North America alone.[1] Its high prevalence rate and course of progression, which result in the individuals being dependent on care from others, make this disease relevant to study. In AD, massive loss of neurons affects several regions of the brain, including the hippocampus and prefrontal cortex, which are involved in memory processes and cognition, thereby causing memory loss and cognitive decline. The role of sex and gender in the disease is interesting because AD is more prevalent and severe in women than in men. There are many factors that can contribute to the differential occurence between the sexes, ranging from lifestyle and genetics to biological metabolism and neuroanatomy. Furthermore, due to the post-mortem diagnosis of the disease, progression or onset of the disease among the different sexes are very challenging to interpret.

Though this observation is not fully understood, it is believed that the gene APOE e4, widely known as a AD risk factor, may increase the inheritance and risk for AD in a sex dependent manner.[2] The innate differences of brain anatomy and biological metabolism in men and women may also be key potential effectors to this differential AD onset when aging.[3], [4]

Significance of Sex and Gender in AD

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Statistics

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Apolipoprotein E4 in Alzheimer's Disease

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed pellentesque ullamcorper ante quis vehicula. Aenean massa odio, placerat eget vehicula id, porta eget mauris. In hac habitasse platea dictumst. Aenean suscipit pellentesque ante. Etiam vel nunc a justo laoreet congue. Phasellus at ullamcorper quam. In mattis sem blandit lectus pharetra ac feugiat nibh ornare. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Suspendisse a risus a lacus feugiat tempor. Morbi sed risus turpis, quis viverra arcu. Fusce vel erat libero. Nam nunc ante, laoreet at tincidunt quis, tempor vel lorem. Integer dapibus pulvinar est, sit amet ultricies orci posuere et. Mauris euismod sagittis sapien quis vulputate. Maecenas mollis massa ac nibh ultricies egestas. Etiam tincidunt, lorem sed bibendum ultricies, orci metus feugiat lacus, sit amet gravida ante mi sit amet metus.

Apolipoprotein E gene polymorphism by Gender

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed pellentesque ullamcorper ante quis vehicula. Aenean massa odio, placerat eget vehicula id, porta eget mauris. In hac habitasse platea dictumst. Aenean suscipit pellentesque ante. Etiam vel nunc a justo laoreet congue. Phasellus at ullamcorper quam. In mattis sem blandit lectus pharetra ac feugiat nibh ornare. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Suspendisse a risus a lacus feugiat tempor. Morbi sed risus turpis, quis viverra arcu. Fusce vel erat libero. Nam nunc ante, laoreet at tincidunt quis, tempor vel lorem. Integer dapibus pulvinar est, sit amet ultricies orci posuere et. Mauris euismod sagittis sapien quis vulputate. Maecenas mollis massa ac nibh ultricies egestas. Etiam tincidunt, lorem sed bibendum ultricies, orci metus feugiat lacus, sit amet gravida ante mi sit amet metus.

ApoE4 and circulating androgen levels

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed pellentesque ullamcorper ante quis vehicula. Aenean massa odio, placerat eget vehicula id, porta eget mauris. In hac habitasse platea dictumst. Aenean suscipit pellentesque ante. Etiam vel nunc a justo laoreet congue. Phasellus at ullamcorper quam. In mattis sem blandit lectus pharetra ac feugiat nibh ornare. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Suspendisse a risus a lacus feugiat tempor. Morbi sed risus turpis, quis viverra arcu. Fusce vel erat libero. Nam nunc ante, laoreet at tincidunt quis, tempor vel lorem. Integer dapibus pulvinar est, sit amet ultricies orci posuere et. Mauris euismod sagittis sapien quis vulputate. Maecenas mollis massa ac nibh ultricies egestas. Etiam tincidunt, lorem sed bibendum ultricies, orci metus feugiat lacus, sit amet gravida ante mi sit amet metus.

ApoE4 and cortical thickness by gender

Impairment in hilar GABAergic interneuron

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Sed pellentesque ullamcorper ante quis vehicula. Aenean massa odio, placerat eget vehicula id, porta eget mauris. In hac habitasse platea dictumst. Aenean suscipit pellentesque ante. Etiam vel nunc a justo laoreet congue. Phasellus at ullamcorper quam. In mattis sem blandit lectus pharetra ac feugiat nibh ornare. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Suspendisse a risus a lacus feugiat tempor. Morbi sed risus turpis, quis viverra arcu. Fusce vel erat libero. Nam nunc ante, laoreet at tincidunt quis, tempor vel lorem. Integer dapibus pulvinar est, sit amet ultricies orci posuere et. Mauris euismod sagittis sapien quis vulputate. Maecenas mollis massa ac nibh ultricies egestas. Etiam tincidunt, lorem sed bibendum ultricies, orci metus feugiat lacus, sit amet gravida ante mi sit amet metus.

Neuroanatomical differences in AD

Hormone therapy responses

Gender-dependent expression of neurotrophin and glutamate receptor in cholinergic basal forebrain and risk of AD

Sex-dependent Atrophy

White matter and gray matter (imaging studies)

Bibliography
2. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nature Reviews Neurology 3,137-152, (2011).
3. Leung, L. et al. Apolipoprotein E4 Causes Age- and Sex-Dependent Impairments of Hilar GABAergic Interneurons and Learning and Memory Deficits in Mice. PLoS ONE 7 12: e53569, (2012).
4. Carter CL, Resnick EM, Mallampalli M, et al. Sex and Gender Differences in Alzheimer’s Disease: Recommendations for Future Research. Journal of Women’s Health 21, 1018- 1023, (2012).

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