Medical, Medical School, Notes

Alzheimer’s Disease: The Untreatable Malady

Alzheimer’s is a brain disease that causes problems with memory, thinking and behavior. People here forgets everything as well as its effects on his lifestyle, even he may forget his address, his identity and so on.

It is normal to forget, but it can lead to extreme illness when it comes to Alzheimer’s disease. It is an extreme progressive disease.

History

One hundred years ago a small group of psychiatrists described the abnormal protein deposits in the brain that define the most common neurodegenerative disease which causes atrophy or shrinkage of the brain & causes brain cell death.

Age of onset

After 60, AD begins to develop but during 30 or 40 it may also develop which is the early onset of AD. Dementia develops before AD. This dementia held for episodes of Depression occurring more than 10 years before. Researches show that 78.5 years age is the mean age for Alzheimer’s disease. It shows that 90% cases occur in late age while only 1-10% occurs in 50-55 years age. The rate increases as the age progresses. Age is a major factor for developing Alzheimer’s disease.

Cause

  • Plaques
  • Tangles

In cell membrane Amyloid precursor protein (app) helps neurons grow & repair which later on gets used & recycled. Enzymes like alpha-secretase & gamma secretase dissolves the protein. But if Beta secretase joins them & leaves some fragments of the following protein which are sticky in nature & bind together forming beta-amyloid plaques outside synapse of the neuron. It may cause inflammation to other surrounding neurons.

Figure: Plaque formation

Inside the microfilaments there are some proteins called Tau protein which maintain stability of the filaments. It is thought that after forming plaques, kinase enzyme leaves phosphate group which changes the shape of filaments & Tau proteins that clump up with one another and get tangled. This characteristic is called Neurofibrillary tangles which results apoptosis means cellular death.

Figure: Shrinkage of brain cells

Here Atrophy or shrinkage of brain cells occurs. The gyri becomes narrower & as a result, sulci (Group between gyri) becomes wider.

Stages:

There are 2 groups:

  1. Sporadic
  2. Familial

a) Sporadic

Risk factors include;

  • Age: Early onset of age is rare. On the other onset of age is very common.
  • Gene: It is thought that a gene is considered to be responsible for Alzheimer’s disease & that is e⁴ Allele apolipoprotein E gene also known as APOE e⁴. APOE helps to breakdown beta amyloid but APOE e⁴ – are more likely to develop beta amyloid plaques.

If a patient has one APOE e⁴ he /she has the chance to develop Alzheimer’s disease. If a patient has two APOE e⁴ he/she has increased chances for developing Alzheimer’s disease.

b) Familial

Mainly causes by several gene mutations. It is said to be the reason for early onset as it requires a lot of dominant genes.

2 genes- PSEN-1 & PSEN-2 situated in respective Chromosome 14 chromosome 1. They both code for presenilin 1 & presenelin 2 which are the subunit of gamma secretase. Mutation of these 2 genes can change the location for cutting of beta amyloid molecules as the position of cutting down of gamma secretase changes. This develops forming plaques more rapidly.

Down Syndrome

Highly binds with down syndrome where Trisomy 21 is responsible for producing extra chromosomes that are located in the APP gene. Here the APP gene has extra 21 Chromosomes which increase again amyloid plaque formation so rapidly. That’s why Alzheimer’s disease is also seen in the patients of down syndrome.

Sign Symptom

Early Signs:

  • Memory loss
  • Changes mood
  • Misplacing belongings
  • Hard to complete familiar tasks
  • Social withdrawal
  • Poor judgement
  • Struggling to communicate

Progressive

  • Memory loss
  • Motor skills loss
  • Language effects
  • Disorientation
  • Bedridden
  • Death

Characteristics

  • Anterograde amnesia is usually first sign
  • Life expectancy increase shows more cases in recent years
  • Zapped (loss of) acetylcholinergic neurons
  • Hereditary disease
  • Entire hippocampus becomes affected
  • Identified by neurofibrillary tangles
  • Mutation in amyloid genes associated with disease
  • Entorhinal areas degenerate first
  • Retrograde amnesia ultimately develops
  • Senile plaques are formed at synapse

Associations

  • Amyloid Beta protein
  • Aluminum toxicity
  • Acetylcholine deficiencies
  • Apolipoprotein gene E
  • Altered nucleus basalis of Meynert
  • Down’s syndrome

Findings

  • Apraxia
  • Actin inclusions (Hirano bodies)
  • Atrophy of brain
  • Amyloid plaques
  • Aphasia
  • Agitation
  • DNA-coiled tangles
  • Dementia
  • Disoriented
  • Depressed

Related Disease

Alzheimer’s disease is seen with Dementia. Forgetting something develops dementia & that may lead to Alzheimer’s disease. Dementia is strongly related with Alzheimer’s disease.

Also there’s a strong connection between Alzheimer’s disease & Diabetes. Alzheimer’s disease increases the possibility & effects of diabetes. It also enhances the rate of Glaucoma. Loss of retinal ganglion cells may develop through Alzheimer’s disease. It also progresses the exhibition of optic nerve degeneration. As age increases, cataract, macular degeneration etc. happens but may have bare relation with Alzheimer’s disease. But the combination of both leads to massive problems.

Diagnosis

It is quite difficult to diagnose Alzheimer’s disease. There is a suitable way to detect this by doing a brain biopsy after performing an autopsy. Also by excluding other causes of dementia it can be diagnosed.

Treatment

Though Alzheimer’s disease doesn’t have any significant Cure, Pharmacological treatment of Alzheimer’s disease is based on the use of acetylcholinesterase inhibitors, which have beneficial effects on cognitive, functional, and behavioral symptoms of the disease.

Recently it is approved drug memantine, an NMDA channel blocker indicated for advanced Alzheimer’s Disease reviewing clinical features of the available cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) including their pharmacological properties.

Now the treatment is more modified & studies as a result now includes amyloid-β-peptide vaccination, secretase inhibitors, cholesterol-lowering drugs, metal chelators, and anti-inflammatory agents

Prevention & awareness

  • Healthy diet
  • Reading books
  • Playing logical games
  • Playing instruments
  • No smoking
  • No alcohol
  • Maintain social circle
  • Praying
  • Exercise