An Introduction to Alzheimer’s & What We Know So Far to Avoid It
By Louise Matthews | Weekly Column: Neuroscience + Society
From the Epic of Gilgamesh in Ancient Mesopotamia to Sun Simia’s Danjing Yaojue, or “Essential Formulas of Alchemical Classics,” to the European motif of the ‘Philosopher’s Stone,’ the quest for an ‘Elixir of Life’ to grant eternal youth is nothing new. While neurodegenerative diseases (NDs) are not an immediate death-sentence, and curing them wouldn’t grant one
immortality, decelerating their development and progression with healthy preemptive habits would prevent the disappearance of identities by nipping dementia in the bud. From an ethical standpoint, it is imperative for beneficial scientific knowledge about ND prevention to be shared
with society.
NDs such as late-onset Alzheimer’s disease (AD) tend to develop later in life after the age of 65 (Koedam et al., 2009). Currently, according to the amyloid hypothesis (Glenner et al., 1984), the scientific community theorizes NDs to be the result of an accumulation of protein aggregates (i.e.
beta amyloid plaques and tau neurofibrillary tangle pathologies) in and around cells, resulting in neuronal and glial death and consequent tissue degeneration (Dugger et al., 2017). Patients suffering from these diseases experience cognitive decline such as dementia and declarative episodic memory loss (Erkkinen et al., 2018). Alarmingly, the number of AD diagnoses has surged in recent years, increasing from three million to five million Americans between 1980 and 2011, and projected to reach 10 million Americans by 2050, according to US census middle series projections (Brookmeyer et al., 2011). The first case of Alzheimer’s was diagnosed at the Hospital for the Mentally Ill and Epileptics in Frankfurt, Germany in 1901 (Enserink, 1998). Consequently, it is thought that the cause of late-onset NDs such as AD must be environmental and lie in the habits of modern life. In fact, with only five percent of Alzheimer’s cases being familial, sporadic cases account for a whopping ninety five percent of patients (Bali et al., 2012). While protein aggregates function as a viable therapeutic target in the future of AD treatment (e.g.: Biogen’s Aducanumab), factors leading to this disease phenotype remain elusive (Zhang et al., 2018). As a result, ways to directly prevent protein aggregation are also unknown. Nevertheless, being that AD is a multifactorial disease involving a variety of pathogenic pathways, a plethora of preventative measures can still be taken to reduce one’s risk of developing AD and to avoid a devastating dementia epidemic.
It has now been established that having hyperinsulinemia or diabetes, a disease in which the body makes insufficient insulin, resulting in high blood glucose, are risk factors for developing AD (Luchsinger et al., 2007). Furthermore, with antidiabetic drugs such as Metformin showing
promising results to improve executive functioning, learning and memory in AD patients, it is likely that the causes of both diseases are strongly connected (Koenig et al., 2017). In fact, one theory postulates that AD is merely ‘type 3 diabetes’ because disturbances in brain insulin and
insulin-like growth factor signaling potentially account for the majority of molecular, biochemical, and histopathological lesions in AD (de la Monte et al., 2007). Exercising regularly and eating a proper diet to prevent diabetes may also be the key to avoiding AD. Dieting in the form of caloric restriction may also be promising in the prevention of NDs.
Beyond increasing longevity in rhesus monkeys by decelerating the onset of age-related physiological changes and diseases (Coleman et al., 2014), caloric restriction without malnutrition has been shown to delay the onset of neurodegeneration in a mouse model with this aging-related phenotype by inducing the expression of a lifespan regulating protein called SIRT1
(Graff et al., 2013). However, without sufficient studies on humans, it remains unclear whether the health benefits of such a diet would outweigh the psychological disadvantages.
It has also been confirmed that there is a bidirectional relationship between sleep and neurodegenerative disease development. Today, one in three adults reports being sleep deprived every single day. Unfortunately, shorter and poorer sleep correlates with greater beta-amyloid burden in regions of the brain associated with AD. (Spira et al., 2013) This is likely due to the combination of increased beta-amyloid protein production from neurons when they are firing during the wakeful state (Nir et al., 2011), and in decreased metabolic clearance via the glymphatic system with less sleep (Benveniste et al., 2019). Moreover, oxidative stress, which corresponds to the toxic build-up of reactive oxygen species in cells, can be induced by extended wakefulness, which downregulates SirT3 antioxidant activity, resulting in apoptosis which may accelerate neurodegeneration (Macedo et al., 2021). To decrease your chances of developing AD, make sure to get the CDC-recommended seven to eight hours of sleep every night.
Finally, for patients at risk of developing AD, taking the anti-inflammatory drug Luteolin, a flavone found in foods such as apples, onions, berries and leafy greens, may prevent the development of the ND. In fact, the deposition of beta-amyloid plaques results in the induction of microglial neuroinflammatory pathways including the secretion of cytokines, sometimes accelerating neurodegeneration. Luteolin can relieve this neuroinflammation aggravating AD by activating the gut microbiota-liver-brain axis to reduce the aggregation of beta-amyloid proteins.
(Daily et al., 2021).
Ultimately, by assuring a diabetes-friendly/anti-inflammatory diet, exercise, and sufficient sleep into your lifestyle, the AD epidemic can be prevented. While some may argue that spontaneously indulging in the pleasures of life is what makes it worth living, these few key changes may be the answer to staying mentally young for as long as time is on your side.
at the Institute for Genomic Medicine by consolidating pilot research showing that autophagy gene
overexpression decelerates protein aggregation in transgenic mice for neurodegenerative diseases.
