Medically Fit For Exams
Medically Fit For Exams

Alzheimer's Disease


The most common cause of dementia in older people


Risk factors

  • Age
  • Family members
  • Diabetes
  • Obesity
  • Cardiovascular risk factors (eg hypertension)
  • Female
  • Head trauma


Differential diagnoses

  • Vascular dementia
  • Parkinsons/Lewy body dementia
  • Stroke
  • Depression
  • Delirium/infection
  • Haemorrhage
  • Tumour



  • Strongly associated with age: 1 in 6 over 80
  • Twice as common in females
  • Worldwide
  • More common in trisomy 21



  • Genetic influences – including APP gene mutations, which increases likelihood of amyloid beta plaques
  • Build up of amyloid beta plaques, Tau tangles and loss of (cholinergic) neurons – leading to brain atrophy


Clinical features

  • Memory loss (episodic first, procedural maintained the longest)
  • Visuospatial disruption
  • Confusion
  • Loss of executive function
  • Dysphasia/speech problems
  • Apraxia
  • Agnosia (recognising objects)
  • Personality remains intact until very late stages



  • Amyloid beta (Aβ) plaques
    • Formed from amyloid precursor protein (APP), which is coded for by a gene on chromosome 21, and is a membrane glycoprotein
    • Is cleaved by α- β- and γ- secretases, which break it down into smaller peptides
    • Aβ-42 is especially likely to aggregate into oligomer tangles, and is cleaved by γ-secretase. This is generally upregulated in AD, as a result of genetic abnormalities
    • Aβ-40 also aggregates, although has more physiological roles
    • Aggregations are formed extracellularly. Microglia attempt to clear/phagocytose these, but can’t and become included
    • Astrocytes and abnormal dendritic processes are become included in the aggregation
    • These are known as amyloid plaques, and develop preferentially in the hippocampus, amygdala, cortex and vessels (amyloid angiopathy)
  • Tau tangles
    • Tau is a protein that is also expressed in healthy cells, and is involved in microtubule structure and function
    • In AD it becomes hyperphosphorylated, and breaks away from the microtubule, forming paired helical filaments
    • These tangle up with each other, and cause cell dysfunction and death, leading to release of the Tau tangles into extracellular space
    • Hyperphosphorylated Tau increases formation of Aβ plaques
    • Similarly Aβ plaques increase the rate of Tau phosphorylation
    • Tau tangles are not unique to AD, they are also involved in other neurodegenerative disorders, collectively known as Tauopathies
  • Neuronal loss
    • AD is characterised by neuronal loss, at least partly as a result of Aβ plaques and Tau tangles
    • Cholinergic neurons are preferentially targeted – so atrophy is greatest in the MTL (hippocampus), basal forebrain and cerebrum
    • Leads to an increase in size of the temporal horns of lateral ventricles
    • Leads to a reducing in ACh concentration in the brain, which is at least partly responsible for the impairments in memory and cognitive function



  • Clinical and MMSE (Mini mental state exam)
  • CT and MRI



  • Acetylcholinesterase inhibitors are used to increase ACh concentration in synaptic clefts, but are symptomatic treatment only
    • Eg Galantamine, Rivastigmine, Donezepil
    • Side effects: nausea, vomiting, diarrhoea, bradycardia, BP disturbance
  • Are currently no disease modifying treatments
    • Immunisation with Aβ is an option that has been intensely researched. It has been found that immunisation early in AD (in humans) and in AD-prone mice significantly reduces or removes Aβ plaques, but this doesn’t lead to any improvement in symptoms
      • Is still an exciting option – maybe immunisation needs to happen BEFORE AD onset?
      • Maybe Aβ plaque development is a result, not a cause, of AD?
  • Lifestyle advice
  • Occupational and educational advice



  • AD is a degenerative disorder, with significant disabling effects
  • Life expectancy after diagnosis is 8 – 10 years, although is very variable
Alzheimer's Disease.docx
Microsoft Word document [17.2 KB]

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