Trey Hughes

ISM – Period 7
Lane, C. A., et al. “Alzheimer's Disease.” European Journal of Neurology, John Wiley & Sons,

Ltd (10.1111), 19 Oct. 2017, onlinelibrary.wiley.com/doi/full/10.1111/ene.13439.

• Alzheimer’s has been identified as a public health epidemic and is of major importance.
While we do know a lot of the pathology behind Alzheimer’s, as well as what may cause
it since its discovery in 1907 by Alois Alzheimer, there has not been a single medication
that is able to alter the disease, only able to slightly mitigate its effects.
• Current studies say that 44 million people across the globe have dementia. This number is
expected to triple by 2050 as more and more people age.
• Around this time, the cost of dementia in the United States is expected to be around $600
billion.
• In western countries, the risk of Alzheimer’s, particular among men, has dropped
recently. It is speculated that this is because of increasing awareness and ability to
manage vascular diseases.
• While it is usually unpredictable, scientists have pinned the mutations of three genes to
the pathology of Alzheimer’s: amyloid precursor protein (APP), presenilin 1 (PSEN1),
and presenilin 2 (PSEN2).
• The majority of Alzheimer’s cases involve the complicated relationship between genetics
and environmental influences and factors. 70% of Alzheimer’s risk is driven by genetics.
• The genetics involved in Alzheimer’s can involve many different types of mutations or
predispositions, such as the metabolism of cholesterol and microglial activation.
• Education and exercise are said to protect against Alzheimer’s, while hypertension and
diabetes are said to increase risk.
• The most distinct characteristics of the pathology of Alzheimer’s are amyloid plaques and
neurofibrillary tangles. Most of the neurofibrillary tangles are made of the tau protein.
This eventually leads to macroscopic atrophy of neurons, causing the brain to shrink in
size.
• The other hypothesis regarding Alzheimer’s pathology is the amyloid hypothesis. This
says that when amyloid beta is clipped, and not cleared, tangles form, leading to
neurodegeneration.
• The link between amyloid beta and tau pathology is unclear at the moment. It is believed
that the immune system plays a role in Alzheimer’s pathology.
• The most often presentation of Alzheimer’s is an old individual with increasing problems
regarding episodic memory.

This article was very educational about the underlying pathology and statistics regarding
dementia and Alzheimer’s, as well as the links between different physiological processes, such
as cardiovascular risk and genetic risk
.
 Trey Hughes
ISM – Period 7
Mendiola-Precoma, J, et al. “Therapies for Prevention and Treatment of Alzheimer's Disease.”

BioMed Research International, Hindawi Publishing Corporation, 2016,

www.ncbi.nlm.nih.gov/pmc/articles/PMC4980501/.

• Alzheimer’s as a disease is characterized by a blood-brain barrier disruption, oxidative

stress, impairment of the mitochondria, inflammation it the brain, and a low metabolic
rate.
• Besides Tau and amyloid beta pathology, decreasing acetylcholine levels and reduced
cerebral blood flow has also been observed in Alzheimer’s patients.
• Pharmaceutical medications can be divided into two distinct groups: symptomatic
treatments and etiology-based treatments.
• Symptomatic medications include acetylcholinesterase inhibitors that stop acetylcholine
from being broken down by enzymes, as well as N-methyl-D-aspartate (NMDA) receptor
antagonists. This group of medication target the peripheral pathology of Alzheimer’s.
• Etiology-based medications include secretase inhibitors, amyloid binders, and tau
therapies. This group of medication target the main pathology of Alzheimer’s as it is
currently understood.
• 95% of people with Alzheimer’s have sporadic or late-onset AD, which is both
influenced and caused by environmental components as well as genetic predisposition to
Alzheimer’s.
• 5% of people with Alzheimer’s have familial or early onset AD, caused by genetic
mutations in the APP gene on chromosome 21, the PSEN-1 gene on chromosome 14, and
the PSEN-2 gene on chromosome 1.
• Other forms of treatment of Alzheimer’s include prevention by way of promoting
exercise, good mental health, socialization, and a healthy diet.
• Diagnosis of Alzheimer’s requires a neuropsychological evaluation according to DSM-V
criteria among with many other groups. Lab tests, MRI scans, and PET scans are also
performed as the disease progresses.
• Many of the pathological findings come from postmortem brains with AD.
• Hypercholesterolemia is considered a risk factor for Alzheimer’s.
• Inhibitors of the phosphorylation of the tau protein such as tideglusib have shown
statistically significant benefits.
• Drugs that treat type II diabetes mellitus have been observed to have a neuroprotective
effect in AD.

This article taught me a lot of interesting details about both the peripheral and main pathology of
Alzheimer’s, as well as how these two different types of pathology are being treated and tested
upon.
 Trey Hughes
ISM – Period 7
Crous-Bou, Marta, et al. “Alzheimer's Disease Prevention: from Risk Factors to Early

Intervention.” Alzheimer's Research & Therapy, BioMed Central, 12 Sept. 2017,

www.ncbi.nlm.nih.gov/pmc/articles/PMC5596480/.

• Some of the modifiable risk factors for Alzheimer’s disease, as highlighted by the US
National Institutes of Health include diabetes mellitus, smoking, depression, mental and
physical inactivity and poor diet as risk factors for cognitive decline and AD.
• A lot of modifiable risk factors related to cardiovascular risk factors, such as diabetes,
hypertension, and obesity.
• It has been proposed that because diabetes disrupts the clearing of amyloid beta
clearance, this in turn causes beta amyloid accumulation.
• Evidence has pointed to the fact that mid-life hypertension can increase the risk of
Alzheimer’s by up to 50%.
• High blood pressure has also been shown to be a risk factor for Alzheimer’s as it could
jeopardize the vascular integrity of the blood-brain barrier.
• Mid-life obesity has been shown to increase Alzheimer’s risk by 60%.
• Smoking can increase risk of Alzheimer’s because of the oxidative stress and
inflammatory responses it causes.
• Studies have shown that increased physical activity also benefits brain health.
• The reason for this is that physical activity can activate brain plasticity, vascularization,
stimulation of neurogenesis, and reducing inflammation levels
• In comparison to sedentary behavior, people with high levels of physical activity have
been shown to halve their risk for Alzheimer’s.
• Mediterranean diets have been shown to protect against cognitive decline and can even
improve memory and mental health in general.
• Social and intellectual activity along with high education have also been shown to
decrease the risk of dementia and Alzheimer’s.
• 20% of Alzheimer’s cases worldwide can be attributed to low-education.
• Bilingualism has been shown to have a beneficial effect on mental health and has even
been shown in studies to delay the onset of dementia by 4 years or so.
• Evidence regarding prevention and avoidance of AD risk factors have been promising on
helping fight the disease.

This article was fundamental for me to understand the modifiable and non-modifiable risk
factors surrounding Alzheimer’s, and the many treatments that are implemented to treat dementia
and Alzheimer’s early.