Alzheimer's disease

ALZHEIMER’S DISEASE

By:

SHIVANI KHODIDAS BBI-III-13007

ASHWINI MUSHUNURI BBI-III-13010

GAYATRI YADAV BBI-III-13014

ALZHEIMER`S DISEASE: Glance of topic

• What is Alzhimer`s Disease?• Unrevaling the mystery.• AD and Brain: pathophisiology and

biochemistry.• Symptoms.• Diagnosis of alzhimer`s disease.• Treatment after diagnosis.• DIET, Management and Prevention.• New research findings.

What is Alzhimer`s Disease? • Alzheimer`s disease(AD) is an incurable

neurological disease in which changes in the nerve cells of the brain result in the death of a large number of cells. This destruction of brain cells eventually leads to serious mental deterioration, dementia, and death.

• Dementia is a broad category of brain diseases that cause long term loss of the ability to think and reason clearly that is severe enough to affect a person's daily functioning.

The brain state of a person having

Alzheimer’s disease

UNREVALING THE MYSTERY• Dr. Aloysius "Alois"

Alzheimer was a Bavarian-born German psychiatrist and neuropathologist and a colleague of Emil Kraepelin.

• Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepelin would later identify as Alzheimer’s disease.

Dr. Aloysius "Alois" Alzheimer

• In 1901, Dr. Alzheimer observed a patient at the Frankfurt Asylum named Auguste Deter. The 51-year-old patient had strange behavioral symptoms, including a loss of short-term memory.

• With two Italian physicians, he used the staining techniques to identify amiloid plaques and neurofibrillary tangles (it is a primary marker of Alzheimer’s Disease).

• Therefore it was named as Alzheimer‘s Disease.

Alois Alzheimer's patient Auguste Deter in 1902.

UNREVALING THE MYSTERY

AD AND BRAINThe Brain of the AD have an abundance of two

abnormal structures:• beta-amyloid plaques, which are dense deposits of

protein and cellular material that accumulate outside and around nerve cells

• neurofibrillary tangles, which are twisted fibers that build up inside the nerve cell

Actual Beta-amyloid plaquesActual tangles

PathophysiologyNeuropathology:

• Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions.

• This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.

• Degeneration is also present in brainstem nuclei like the locus coeruleus.

• Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.

Pathophysiology• Plaques are dense, mostly insoluble

deposits of beta-amyloid peptide and cellular material outside and around neurons.

• Tangles (neurofibrillary tangles) are

aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves.

Histopathologic image of senile plaques seen in the cerebral cortex of a person with Alzheimer's disease of presenile onset. Silver impregnation.

Studies using MRI and PET have documented reductions in the size of specific brain regions in people with AD as they progressed from mild cognitive impairment to Alzheimer's disease.

Pathophysiology

Biochemistry• Alzheimer's disease has been identified as a

protein misfolding disease (proteopathy), caused by plaque accumulation of abnormally folded beta amyloid and tau amyloid proteins in the brain.

• AD is also considered a tauopathy due to abnormal aggregation of the tau protein.

• A protein called tau stabilises the microtubules when phosphorylated, and is therefore called a microtubule-associated protein.

Biochemistry• In AD, tau undergoes chemical changes, becoming

hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system.

1 3

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Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of senile plaques in AD.

Biochemistry

The role of plaques and tangles : • Plaques and tangles tend to spread through the

cortex as Alzheimer's progresses.

Take the Brain Tour :

• Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells.

• Plaques are deposits of a protein fragment called beta-amyloid (BAY-tuh AM-uh-loyd) that build up in the spaces between nerve cells.

• Tangles are twisted fibers of another protein called tau (rhymes with “wow”) that build up inside cells.

Biochemistry

Biochemistry• Though most people develop some plaques and

tangles as they age, those with Alzheimer's tend to develop far more. They also tend to develop them in a predictable pattern, beginning in areas important for memory before spreading to other regions.

• Scientists do not know exactly what role plaques and tangles play in Alzheimer's disease. Most experts believe they somehow play a critical role in blocking communication among nerve cells and disrupting processes that cells need to survive.

• It's the destruction and death of nerve cells that causes memory failure, personality changes, problems carrying out daily activities and other symptoms of Alzheimer's disease.

Symptoms• During the first two to four years, people with

Alzheimer’s disease generally experience loss of memory for recent events, and disorientation.

• Later, the person will often have problems with progressive memory loss, judgment, concentration and speech.

• Loss of physical abilities, similar to that seen in Parkinson's disease, occurs in a small proportion of affected people.

Symptoms• At this point, the person may forget

to take a bath and will have problems with once-routine chores.

• People with Alzheimer’s may also suffer sleeplessness, “sundowning” (confusion or agitation in the evening hours), and perseveration (repetition of the same ideas, words, movements, or thoughts).

• Final stage disease progression includes severe problems with eating, communication, and control of bodily functions.

Symptoms

Diagnosis of Alzheimer’s Disease

• Alzheimer's disease is usually diagnosed based on the person's history, history from relatives, and observations of the person's behaviours.

• The diagnosis include test like eye-drop test, genetic tests, spinal fluid tests, various types of neuropsychologic or cognitive tests, and brain imaging tests.

• Advanced medical imaging with computed tomography and with single-photon emission computed tomography (SPECT).

DEIT• People who eat a mediterranean diet have a lower risk of AD,

and it may improve outcomes in those with the disease.• There is tentative evidence that caffeine may be protective.• A number of foods high in flavonoids such as cocoa, red wine,

and tea may decrease the risk of AD.

ManagementThere is no cure for Alzheimer's disease;

available treatments offer relatively small

symptomatic benefit but remain palliative in nature.

DEIT and Management

Prevention• At present, there is no definitive evidence to

support that any particular measure is effective in preventing AD.

• Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results.

• Epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing AD.

Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.

Prevention

Treatment After Diagnosis

• New drugs for the treatment of AD are now available.

• These drugs increase the brain levels of acetylcholine, a chemical involved in memory functions.

• The first of the drugs approved, Tacrine, requires frequent blood tests for monitoring.

• More recently, Donepezil (Aricept) was also approved by the FDA.

• These drugs do not cure Alzheimer's or stop its progression, but may provide some symptomatic benefit.


• The person with Alzheimer’s will need good medical follow-up throughout the course of the disease.

• If he/she experiences delusions or great psychological stress, careful use of drugs to treat these symptoms may be indicated.

• The life span of someone with Alzheimer’s can range from under five to more than twenty years

• Families caring for a loved one with end-stage Alzheimer’s should give thoughtful consideration to placement in a skilled nursing facility where adequate management and supervision can be provided.


New Research Finding

• New developments in genetic research into Alzheimer’s disease have recently come to light.

• For a number of years, investigators have known that there is a genetic connection in some cases of Alzheimer’s disease, namely an abnormality on Chromosome 21 which results in Down’s Syndrome.

• Chromosome 21 carries the gene for amyloid percursor protein (APP).

• This large protein is broken down into beta amyloid which is thought to be the source of senile plaques in the brains of people with Alzheimer's disease.


• It has been shown that mutations of the APP gene can lead to the development of Alzheimer's disease at a young age, typically in a person's fifties.

• Other genetic developments include the discovery on Chromosome 14 of the specific gene responsible for the cases of familial early onset AD.

• was identified and linked to the type of AD found in people descended from Germans who lived in Russia near the Volga River.

• This gene and the protein it produces share a number of similarities with the Chromosome 14 gene. Again, this is a very rare mutation.

• A fourth gene, located on Chromosome 19, codes for a protein called APOE.

• APOE4 is important because it is the first discovery of a potential mechanism for the development of Alzheimer’s disease.

• The presence of two copies of the APOE4 gene confers a high risk of developing the illness in families with genetically transmitted late-onset Alzheimer’s disease.

• The APOE4 gene is considered a susceptibility gene, not a disease gene, since not all persons who have the gene get the disease and some people may get the disease without having the gene.


• A test to assess the APOE4 gene is available.

• It cannot be used to predict who will develop late-onset AD for anyone not yet showing symptoms of the disease.

• There are still only limited treatment options for this illness, so test results must be placed in the context of accurate information and careful communication and counseling.


New Research Finding• One area of clinical research is focused on treating

the underlying disease pathology.

• Reduction of beta-amyloid levels is a common target of compound(such as apomorphine) under investigation.

• Immunotherapy or vaccination for the amyloid

protein is one treatment modality under study.

• It is based upon the concept of training the immune system to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease.

• In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with methylthioninium chloride (trade name rember), a drug that inhibits tau aggregation, and dimebon, an antihistamine. The consecutive phase-III trial of dimebon failed to show positive effects in the primary and secondary endpoints.

• The common herpes simplex virus HSV-1 has been found to colocate with amyloid plaques.[262] This suggested the possibility that AD could be treated or prevented with antiviral medication.

• Manned spaceflight may harm the brain of astronauts and accelerate the onset of Alzheimer's disease.



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Alzheimer's disease