Disorders with Complex Genetics

Alzheimer’s Disease

Abstract
Alzheimer's is the most common form of dementia, a general term for memory
loss and other intellectual abilities serious enough to interfere with daily life.
Alzheimer's disease accounts for 60 to 80 percent of dementia cases.
Alzheimer's is a type of dementia that causes problems with memory, thinking
and behavior. Symptoms usually develop slowly and get worse over time,
becoming severe enough to interfere with daily tasks
In its early stages, memory loss is mild, but with late-stage Alzheimer's,
individuals lose the ability to carry on a conversation and respond to their
environment

Who gets early onset Alzheimer's?

Many people with early onset are in their 40s and 50s. They have families,
careers or are even caregivers themselves when Alzheimer's disease strikes. In
the United States, it is estimated that approximately 200,000 people have early
onset.
Diagnosing early onset Alzheimer’s:
Since health care providers generally don't look for Alzheimer's disease in
younger people, getting an accurate diagnosis of early onset Alzheimer's can be a
long and frustrating process. Symptoms may be incorrectly attributed to stress
or there may be conflicting diagnoses from different health care professionals.
People who have early onset Alzheimer's may be in any stage of dementia – early
stage, middle stage or late stage. The disease affects each person differently and
symptoms will vary.
If you are experiencing memory problems:
Keep in mind that there is no one test that confirms Alzheimer's disease. A
diagnosis is only made after a comprehensive medical evaluation.
Effects of Alzheimer’s

Alzheimer's disease is one of the costliest chronic diseases to society.

 Nearly one in every five Medicare dollars is spent on people with Alzheimer's
and other dementias.

Typical age-related memory loss and other changes compared to Alzheimer's

 Signs of Alzheimer's
 Typical age-related changes
 Poor judgment and decision making
 Making a bad decision once in a while
 Inability to manage a budget
 Missing a monthly payment
 Losing track of the date or the season
 Forgetting which day it is and remembering later
 Difficulty having a conversation
 Sometimes forgetting which word to use
 Misplacing things and being unable to retrace steps to find them
 Losing things from time to time
Have more time to plan for the future–
A diagnosis of Alzheimer's allows you to take part in decisions about care,
transportation, living options, financial and legal matters. You can also
participate in building the right care team and social support network.
Help for you and your loved ones –
Care and support services are available, making it easier for you and your family
to live the best life possible with Alzheimer’s or dementia.
When you see your doctor
Your doctor will evaluate your overall health and identify any conditions that
could affect how well your mind is working. Your doctor may refer you to a
specialist such as a:
 Neurologist– specializes in diseases of the brain and nervous system
 Psychiatrist – specializes in disorders that affect mood or the way the mind
works
 Psychologist – has special training in testing memory and other mental
functions
 Geriatrician – specializes in the care of older adults and Alzheimer's disease
What are the stages of Alzheimer's?
Alzheimer's disease typically progresses slowly in three general stages — mild
(early-stage), moderate (middle-stage), and severe (late-stage). Since Alzheimer's
affects

people in different ways, each person will experience symptoms - or progress

through Alzheimer's stages - differently.
Overview of disease progression:
 Mild Alzheimer's (early-stage)
 Moderate Alzheimer's (middle-stage)
 Severe Alzheimer's (late-stage)
Mild Alzheimer's disease (early-stage):
Although the onset of Alzheimer's disease cannot yet be stopped or reversed, an
early diagnosis can allow a person the opportunity to live well with the disease
for as long as possible and plan for the future.In the early stages of Alzheimer's,
a person may function independently. He or she may still drive, work and be part
of social activities. Despite this, the person may feel as if he or she is having
memory lapses, such as forgetting familiar words or the location of everyday
objects.
Friends, family or neighbors begin to notice difficulties. During a detailed
medical interview, doctors may be able to detect problems in memory or
concentration.
Common difficulties include:
 Problems coming up with the right word or name
 Trouble remembering names when introduced to new people
 Having greater difficulty performing tasks in social or work settings
 Forgetting material that one has just read
 Losing or misplacing a valuable object
 Increasing trouble with planning or organizing
Moderate Alzheimer's disease (middle-stage):
During the moderate stage of Alzheimer's, individuals may have greater difficulty
performing tasks such as paying bills, but they may still remember significant
details about their life.
Moderate Alzheimer's is typically the longest stage and can last for many years.
As the disease progresses, the person with Alzheimer's will require a greater level
of care.

You may notice the person with Alzheimer's confusing words, getting frustrated
or angry, or acting in unexpected ways, such as refusing to bathe. Damage to
nerve cells in the brain can make it difficult to express thoughts and perform
routine tasks.
At this point, symptoms will be noticeable to others and may include:
 Forgetfulness of events or about one's own personal history
 Feeling moody or withdrawn, especially in socially or mentally challenging
situations
 Being unable to recall their own address or telephone number or the high
school or college from which they graduated
 Confusion about where they are or what day it is
 The need for help choosing proper clothing for the season or the occasion
 Trouble controlling bladder and bowels in some individuals
 Changes in sleep patterns, such as sleeping during the day and becoming
restless at night
 An increased risk of wandering and becoming lost
 Personality and behavioral changes, including suspiciousness and delusions
or compulsive, repetitive behavior like hand-wringing or tissue shredding
Advanced Alzheimer’s Disease (late-stage):
Late-stage care decisions can be some of the hardest families face. Connect with
other caregivers who have been through the process on our online message
boards and get helpful resources in our Caregiver Center.

In the final stage of this disease, individuals lose the ability to respond to their
environment, to carry on a conversation and, eventually, to control movement.
They may still say words or phrases, but communicating pain becomes difficult.
As memory and cognitive skills continue to worsen, personality changes may
take place and individuals need extensive help with daily activities.
At this stage, individuals may:
 Require full-time, around-the-clock assistance with daily personal care
 Lose awareness of recent experiences as well as of their surroundings
 Require high levels of assistance with daily activities and personal care
 Experience changes in physical abilities, including the ability to walk, sit and,
eventually, swallow
 Have increasing difficulty communicating
 Become vulnerable to infections, especially pneumonia
Genetic Testing
Genetic tests are available for both APOE-e4 and the rare genes that directly
cause Alzheimer’s. However, health professionals do not currently recommend
routine genetic testing for Alzheimer’s disease. Testing for APOE-e4 is sometimes
included as a part of research studies.
Risk genes increase the likelihood of developing a disease, but do not guarantee
it will happen. Scientists have so far identified several risk genes implicated in
Alzheimer's disease. The risk gene with the strongest influence is called Apo
lipoprotein E-e4 (APOE-e4). Scientists estimate that APOE-e4 may be a factor in
20 to 25 percent of Alzheimer's cases.
APOE-e4 is one of three common forms of the APOE gene; the others are APOE-
e2 and APOE-e3. Everyone inherits a copy of some form of APOE from each
parent. Those who inherit APOE-e4 from one parent have an increased risk of
Alzheimer’s. Those who inherit APOE-e4 from both parents have an even higher
risk, but not a certainty.
Scientists are not yet certain how APOE-e4 increases risk. In addition to raising
risk, APOE-e4 may tend to make Alzheimer's symptoms appear at a younger age
than usual .Deterministic genes directly cause a disease, guaranteeing that
anyone who inherits them will develop the disorder. Scientists have discovered
variations that directly cause Alzheimer’s disease in the genes coding three
proteins: amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2
(PS-2).
When Alzheimer’s disease is caused by these deterministic variations, it is called
“autosomal dominant Alzheimer’s disease (ADAD)” or “familial Alzheimer’s
disease,” and many family members in multiple generations are affected.
Symptoms nearly always develop before age 60, and may appear as early as a
person's 30s or 40s. Deterministic Alzheimer's variations have been found in
only a few hundred extended families worldwide. True familial Alzheimer’s
accounts for less than 5 percent of cases.
Steps to diagnosis:
There is no single test that can show whether a person has Alzheimer's. While
physicians can almost always determine if a person has dementia, it may be
difficult to determine the exact cause.
Diagnosing Alzheimer's requires careful medical evaluation, including:
 A thorough medical history
 Mental status testing
 A physical and neurological exam
 Tests (such as blood tests and brain imaging) to rule out other causes of
dementia-like symptoms
People with memory loss or other possible warning signs of Alzheimer's may find
it hard to recognize they have a problem and may resist following up on their
symptoms. Signs of dementia may be more obvious to family members or friends.
Having trouble with memory does not mean you have Alzheimer's. Many health
issues can cause problems with memory and thinking. When dementia-like
symptoms are caused by treatable conditions — such as depression, drug
interactions, thyroid problems, excess use of alcohol or certain vitamin
deficiencies — they may be reversed during the medical workup, your health
care provider will review your medical history. He or she will want to know about
any current and past illnesses, as well as any medications you are taking. The
doctor will also ask about key medical conditions affecting other family members,
including whether they may have had Alzheimer's disease or related dementias.
Treatment Horizon:
The science of Alzheimer's has advanced to show potential underlying drivers of
the disease. And we have candidate drugs we can test because of this basic
science knowledge." - Richard Mohs, Ph.D.
A worldwide quest is under way to find new treatments to stop, slow or even
prevent Alzheimer's. Because new drugs take years to produce from concept to
market—and because drugs that seem promising in early-stage studies may not
work as hoped in large-scale trials—it is critical that Alzheimer's and related
dementias research continue to accelerate. To ensure that the effort to find better
treatments receives the focus it deserves, the Alzheimer's Association funds
researchers looking at new treatment strategies and advocates for more federal
funding of Alzheimer's research.
The hope for future drugs:
Currently, there are five FDA-approved Alzheimer's drugs that treat the
symptoms of Alzheimer's — temporarily helping memory and thinking problems
in about half of the people who take them. But these medications do not treat
the underlying causes of Alzheimer's.
In contrast, many of the new drugs in development aim to modify the disease
process itself, by impacting one or more of the many wide-ranging brain changes
that Alzheimer's causes. These changes offer potential "targets" for new drugs to
stop or slow the progress of the disease. Many researchers believe successful
treatment will eventually involve a "cocktail" of medications aimed at several
targets, similar to current state-of-the-art treatments for many cancers and
AIDS. Sign up for our weekly e-news and stay up-to-date on the latest advances
in Alzheimer's treatments, care and research.
CONCLUSIONS
Over the last 30 years, researchers have made remarkable progress in
understanding healthy brain function and what goes wrong in Alzheimer's
disease. The following are examples of promising targets for next-generation drug
therapies under investigation in current research studies:
Beta-amyloid is the chief component of plaques, one hallmark Alzheimer's brain
abnormality. Scientists now have a detailed understanding of how this protein
fragment is clipped from its parent compound amyloid precursor protein (APP) by
two enzymes — beta-secretase and gamma-secretase. Researchers are developing
medications aimed at virtually every point in amyloid processing. This includes
blocking activity of both enzymes; preventing the beta-amyloid fragments from
clumping into plaques; and even using antibodies against beta-amyloid to clear it
from the brain. Several clinical trials of investigational drugs targeting beta-
amyloid are included below in the key clinical trial summary.
Tau protein is the chief component of tangles, the other hallmark brain
abnormality. Researchers are investigating strategies to keep tau molecules from
collapsing and twisting into tangles, a process that destroys a vital cell transport
system.
Inflammation is another key Alzheimer's brain abnormality. Scientists have
learned a great deal about molecules involved in the body's overall inflammatory
response and are working to better understand specific aspects of inflammation
most active in the brain. These insights may point to novel anti-inflammatory
treatments for Alzheimer's disease.
Insulin resistance and the way brain cells process insulin may be linked to
Alzheimer's disease. Researchers are exploring the role of insulin in the brain
and closely related questions of how brain cells use sugar and produce energy.
These investigations may reveal strategies to support cell function and stave off
Alzheimer-related changes.
Reference
 Biological Science: Third Edition By, N. P. O. Green (Author), G. W. Stout
(Author), D. J. Taylor (Author), R. Soper (Editor)
 Exploring Biology By, Ella Thea Smith
 NCERT Text Book
 Tell Me Why
 Encyclopaedia Britannica
Acknowledgement
I would like to express my special thanks of gratitude to my teacher
Mr.S.Balaiyan as well as our principal Mr.Feroz Ratsing who gave me
the golden opportunity to do this wonderful project on the topic
Alzheimer’s Disease , which also helped me in doing a lot of Research and
I came to know about so many new things I am really thankful to them.
Secondly I would also like to thank my parents and friends who helped
me a lot in finalizing this project within the limited time frame.