Abstract
Aging is a risk factor for a number of “age-related diseases”, including Alzheimer’s disease (AD). AD affects more than a third of all people over the age of 85, and is the leading cause of dementia worldwide. Symptoms include forgetfulness, memory loss, and cognitive decline, ultimately resulting in the need for full-time care. While there is no cure for AD, pharmacological approaches to alleviate symptoms and target underlying causes of the disease have been developed, albeit with limited success. This review presents the age-related, genetic, and environmental risk factors for AD and proposes a hypothesis for the mechanistic link between genetics and the environment. In short, much is known about the genetics of early-onset familial AD (EO-FAD) and the central role played by the Aβ peptide and protein misfolding, but late-onset AD (LOAD) is not thought to have direct genetic causes. Nonetheless, genetic risk factors such as isoforms of the protein ApoE have been identified. Additional findings suggest that air pollution caused by the combustion of fossil fuels may be an important environmental risk factor for AD. A hypothesis suggesting that poor air quality might act by disrupting protein folding homeostasis (proteostasis) is presented.
Highlights
Aging is a risk factor for a number of “age-related diseases”, including Alzheimer’s disease (AD)
The strongest and most consistent risk factor for late-onset AD (LOAD) is the presence of the ε4 allele of the apolipoprotein gene (APOE) such that carriers of the ε4 allele are at a nearly 12-fold increased risk of the disease compared to the general population [21]
If ApoE acts through Aβ to increase the risk of AD in an allele-dependent manner, should an additive effect not be observed in patients carrying early-onset familial AD (EO-FAD) mutations? Consistent with this, a recent study of patients with mutations in presenilin 1 revealed that the age of onset of disease symptoms was delayed in patients carrying the protective APOE ε2 allele [27]
Summary
Jean Calment of Arles, France lived to be 122 years old, making hers the longest confirmed lifespan of any human being. Healthy aging involves maximizing lifespan while minimizing age-related medical conditions, and is thereby correlated with a high quality of life. Without a cure on the horizon, the number of people with AD or other age-related dementias will increase substantially over the 20 years. This is partly because the baby boomer generation is just starting to reach retirement age. In addition to impacting earning potential and the ability to save for their own retirement, family members of AD patients serving as caregivers suffer their own array of comorbidities, resulting in a declining health-related quality of life and an increasing number of emergency room visits as compared to non-caregivers [10]. Much recent research has focused on elucidating the molecular mechanisms underlying AD, which has led to new treatment regimens as described below
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
