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Alzheimer Disease
By Ashley Wallace
Facts
• Discovered by Alois Alzheimer in 1907
• 2/3 or more of all diagnosed cases of dementia
are Alzheimer cases
• 100,000 people die each year from it
• 4th leading cause of death after heart disease,
cancer and stroke
Dementia
• The deterioration of intellectual capabilities, memory,
judgment and personality to the extent that daily
functioning and quality of life are seriously impaired.
• Generally affects elderly, but is not confined to this age
group
• Some other circumstances causing dementia include
Huntington Disease, Parkinson Disease, head injury,
multiple strokes, alcoholism, and others.
Symptoms of Alzheimer Disease
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Inability to make new memories
Loss of short term memories
Ability to concentrate and recall past events worsens
Loss of accurate sense of time, and inability to relay the year, day
or month
Sentence formation and coherent verbal communication
diminish
Personality Change
50% suffer from delusions
In the end AD patients are mute immobilized and
uncomprehending
Death is often the result of respiratory failure
3 Neuropathological Features of an
AD patients Brain
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Devastating losses of synapses and neurons within
the hippocampus and the entorhinal cortex.
Dense spherical structures called senile plaques are
prevalent outside the neurons of the hippocampus
and other regions of the brain.
Aggregations of fibrils called neurofibrillary tangles
accumulate within the cell bodies and dendritic
processes of the neurons of the hippocamupus.
http://www.ahaf.org/alzdis/about/AmyloidPl
aques.htm
http://web.lemoyne.edu/~hevern/psy340/graph
ics/alzheimer.normal.brain.jpg
Senile Plaque
• Extracellular deposits of amyloid in the grey matter of the brain.
• The core is a densely packed fibrous structure that is called
amyloid body.
• These are mainly made up of protein.
• Principle protein is a 4kDa peptide (ΑΒ protein; Β protein; Α4,
Β/Α4).
• ΑΒ protein consists of isoforms that range from 39-43 amino
acids
• There are at least 13 other proteins that form these that are
associated with diseases that do not in any way resemble AD
• They have different core proteins but the structures appears
microscopically the same.
• Sequence analysis of isolated clones of ΑΒ40 sequence
showed that the ΑΒ isoforms of senile plaques are derived
by proteolytic cleavage from a larger protein that was called
amyloid precursor protein (APP).
• The APP has a single transmembrane domain and 3
isoforms with 695, 751, 770 amino acids.
• Some of the APP molecules are found in the membrane at
the terminal ends of axons and other intracellular membranes
Fig 14.9
Neurofibrillary tangles
• The main fibrous elements are numerous paired helical filaments
(PHFs) which consist of 2 cross-linked, intertwined protein
strands with each made up of joined tau protein molecules
making the tau filament.
• Tau protein binds to tubluin molecules and facilitates the
assembly of tubulin into microtublules and maintains their
stability
• Tau molecules under abnormal conditions in the NFTs are
hyperphophorylated.
• This cause them not to bind to tubulin but attache to other
microtubule associated proteins.
• This is thought that the new tau molecules block the formation
of microtubules and undermine the stability of existing
microtubules.
References
• Human molecular genetics.Hohn Wiley & Sons,
Inc., Hoboken , NJ. 2005. pp 404-408
• http://www.ahaf.org/alzdis/about/AmyloidPla
ques.htm
• http://web.lemoyne.edu/~hevern/psy340/grap
hics/alzheimer.normal.brain.jpg