Question

Summarize the main neural pathologic changes involved in the etiology of AD (e.g., definitions of neuritic plaques and neurofibrillary tangles and how they form) and the main neurotransmitter “deficiency” that seems to account for most of the signs and symptoms.

Answer 1

Alzheimers Disease is a neurodegenerative disease and is most common cause of dementia in older individuals.

Incidence: Seen commonly in older people, but sometimes individuals in the age group of 40 to 50 yrs also get the disease.

Etiology of Alzheimers disease:

• Old age
• Factors that contribute to the loss of neurons and synapses such as improper diet, unfavourable environment at home etc.
• Diabetis Mellitus
• Traumatic brain injury
• Vasular diseases.

Pathogenesis involved in Alzheimer's Disease are: Pathological changes include 2 types which have positive and negative features.

Extracellular deposition of A-beta amyloid and intracellular accumulation of TAU protien affects specific subclasses of neuron and brain circuits.The A-beta plaques result in localized damage to dendrites, axonal process and synapses. The A-beta plaques include part of the transmembrane domain of Amyloid percussor protien and is derieved by the enzymes beta and gamma secretase. The A-beta monomers polymerize first into soluble oligomers and then into larger insoluble fragments such as A-beta 42 which then precipitates as amyloid fibrils.

Intracellular accumulation of TAU occurs by the neurofibrillary degeneration which is featured by the neural body and insoluble polymers over-phosphorylated microtubule associated with protien tau.

Pathology of Alzheimers Disease: There are 2 main lesions, namely: Senile plaques and Neurofibrillary tangles.

Senile plaques: These are lesions spherical in nature which is present within the cerebral cortex.

• There are 2 main senile plaques, namely: Diffuse A-beta plaque and neuritic plaque.
  • Neuritic plaques and the A-beta plaques contain degenrative neural processes with tau filaments.
  • Neuritic plaques contain astrocytes and microglia.
  • A-beta plaques forms central core which has fibrillary fine structure
  • A-beta plaques do not distract the neurophils

Neurofibrillary tangles: They are the deposits of tau filaments which are present in the neural body. The mechanism of accumulation of tau is very much unclear,but it is understood that the primary lesion in the Alzhiemers disease is A-beta deposition and secondary lesion is neurofibrillary tangles.Analysis of the patterns of neurofibrillary tangles and neuritic plaques deposition suggests that changes appear first in the transentorhinal region of temporal lobe, letral to hippocampus, then to entorhinal cortex, hippocampus, and association neocortex.

Thus the pathology of neurofibrillary tangles consist of 3 stages: transentorhinal, limbic and isocortical.

Neurofibrillary tangles in the hippocampus and the entorhinal cortex are the main neurotransmittor that relates to impairement of memory and cognitive decline.

Symptoms involved:

• Loss of memory
• Loss of ability to learn newer things
• Depression
• Delusion
• Unable to do calculations

Diagnostic evaluation:

• Increase of tau protien and decrease of A-beta in the CSF indicates Alzhimers disease.
• Neuroimaging markers can be used.

Managament:

• Educate the patient and relatives on how to care for the patient.
• Involve the patient in as many activities which improves the patient cognitive condition.
• Regular medications to be administered as advised by the doctor.
• Keep patient always in a safe environment.