Alzheimer

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Alzheimers Disease

• A Geriatric Epidemic

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Alzheimers Disease

• Alzheimers disease currently affects between two
  and four million Americans.
• Causes the degeneration of the nervous system
  over time
• Two basic forms
• Early onset (under 65)
• Late onset (65)

3
History

• The first person to make a diagnosis of
  Alzheimers disease was Alois Alzheimer
  (1864-1915). Alzheimer made the diagnosis on a
  fifty-one year old named Frau Auguste D.
• A Belgian pathologist found amyloid to be a
  component of the plaques found in the brains of
  those with Alzheimers in the 1930s.

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Symptoms

• Asking the same questions over and over again.
• Repeating the same story, word for word, again
  and again.
• Forgetting how to cook, or how to make repairs,
  or how to perform activities that were done with
  ease and regularity.
• Getting lost in familiar surroundings, or
  misplacing household items.
• Neglecting to complete everyday hygiene tasks.
• Relying on someone else to make easy decisions.

5
Treatment

• The drug tacrine helps to slow the degeneration
  process, but it is costly and causes numerous
  side effects including the buildup of the toxic
  liver enzyme alanine aminotransferase.
• Like tacrine, other drugs can only delay the
  inevitable.
• To date there is no cure for Alzheimers disease.

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Alzheimers Physiology

• Alzheimers disease is characterized by the
  presence of amyloid plaques and neurofibrillary
  tangles within the central nervous system.
• The neurofibrillary tangles arrive as the result
  of defective tau proteins.
• The plaques are derived from the buildup of
  ß-amyloid protein, which in turn comes from
  amyloid precursor protein (APP).

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Tau Proteins

• Healthy tau proteins help to support microtubules
  in neurons.
• Mutations on exon 10 on the mRNA strand coding
  for tau gives rise to 3 tau isoforms with four
  microtubule binding site instead of the usual
  three.
• This interferes with the taus ability to
  interact with the microtubule. Instead the free
  tau begins to interact with itself and begins
  building tangles.

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Neurofibrillary Tangle Formation
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ß-Amyloid Plaques

• ß-Amyloid is made from post-translational amyloid
  precursor protein (APP).
• Two different enzymatic pathways exist for APP.
• Three different pathways exist for the site of
  APP digestion and the formation of ß-amyloid.
• The formation of intracellular pools of ß-amyloid
  contributes to the plaques characteristic of
  Alzheimers.

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Enzymatic Pathways
-Aß40 vs. Aß42
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Three Sites of APP Digestion
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Mutations Contributing to Plaques

• Val717 mutation increases ratio of Aß42 to Aß40
• Swedish mutation mutation of amino acid 670 on
  APP from lysine to methionine along with amino
  acid 671 going from asparagine to lysine
  increases use of ß-secretase pathway
• Presenilin mutation increases ratio of Aß42 to
  Aß40

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Cell Death
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The Effect of Plaques on Action Potentials in the
Nervous System
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Closing Comments

• Current research is looking to telomerase for a
  possible cure for Alzheimers.
• Pathologists also hope that stem cells may
  provide a cure.
• Alzheimers not only affects the patients but
  their families as well. It is a sad slow course
  that leaves relatives emotionally exhausted.

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The End