Alzheimer DiseaseAlzheimer DiseaseBy Ashley WallaceBy Ashley Wallace

FactsFacts

• Discovered by Alois Alzheimer in Discovered by Alois Alzheimer in 19071907

• 2/3 or more of all diagnosed cases of 2/3 or more of all diagnosed cases of dementia are Alzheimer casesdementia are Alzheimer cases

• 100,000 people die each year from it100,000 people die each year from it• 44thth leading cause of death after heart leading cause of death after heart

disease, cancer and strokedisease, cancer and stroke

DementiaDementia

• The deterioration of intellectual capabilities, The deterioration of intellectual capabilities, memory, judgment and personality to the memory, judgment and personality to the extent that daily functioning and quality of extent that daily functioning and quality of life are seriously impaired.life are seriously impaired.

• Generally affects elderly, but is not confined Generally affects elderly, but is not confined to this age groupto this age group

• Some other circumstances causing dementia Some other circumstances causing dementia include Huntington Disease, Parkinson include Huntington Disease, Parkinson Disease, head injury, multiple strokes, Disease, head injury, multiple strokes, alcoholism, and others. alcoholism, and others.

Symptoms of Alzheimer Symptoms of Alzheimer DiseaseDisease

• Inability to make new memoriesInability to make new memories• Loss of short term memoriesLoss of short term memories• Ability to concentrate and recall past events Ability to concentrate and recall past events

worsensworsens• Loss of accurate sense of time, and inability to Loss of accurate sense of time, and inability to

relay the year, day or monthrelay the year, day or month• Sentence formation and coherent verbal Sentence formation and coherent verbal

communication diminishcommunication diminish• Personality ChangePersonality Change• 50% suffer from delusions50% suffer from delusions• In the end AD patients are mute immobilized and In the end AD patients are mute immobilized and

uncomprehendinguncomprehending• Death is often the result of respiratory failureDeath is often the result of respiratory failure

3 Neuropathological 3 Neuropathological Features of an AD patients Features of an AD patients

BrainBrain1.1. Devastating losses of synapses and neurons Devastating losses of synapses and neurons

within the hippocampus and the entorhinal within the hippocampus and the entorhinal cortex.cortex.

2.2. Dense spherical structures called senile Dense spherical structures called senile plaques are prevalent outside the neurons of plaques are prevalent outside the neurons of the hippocampus and other regions of the the hippocampus and other regions of the brain.brain.

3.3. Aggregations of fibrils called neurofibrillary Aggregations of fibrils called neurofibrillary tangles accumulate within the cell bodies tangles accumulate within the cell bodies and dendritic processes of the neurons of the and dendritic processes of the neurons of the hippocamupus.hippocamupus.

http://www.ahaf.org/alzdis/about/AmyloidPlaques.htm

http://web.lemoyne.edu/~hevern/psy340/graphics/alzheimer.normal.brain.jpg

Senile PlaqueSenile Plaque• Extracellular deposits of amyloid in the grey matter of Extracellular deposits of amyloid in the grey matter of

the brain.the brain.• The core is a densely packed fibrous structure that is The core is a densely packed fibrous structure that is

called amyloid body. called amyloid body. • These are mainly made up of protein.These are mainly made up of protein.• Principle protein is a 4kDa peptide (Principle protein is a 4kDa peptide (ΑΒΑΒ protein; protein; ΒΒ

protein; protein; ΑΑ4, 4, ΒΒ//ΑΑ4).4).• ΑΒΑΒ protein consists of isoforms that range from 39-43 protein consists of isoforms that range from 39-43

amino acidsamino acids• There are at least 13 other proteins that form these There are at least 13 other proteins that form these

that are associated with diseases that do not in any that are associated with diseases that do not in any way resemble ADway resemble AD

• They have different core proteins but the structures They have different core proteins but the structures appears microscopically the same.appears microscopically the same.

• Sequence analysis of isolated clones of Sequence analysis of isolated clones of ΑΒΑΒ40 40 sequence showed that the sequence showed that the ΑΒΑΒ isoforms of isoforms of senile plaques are derived by proteolytic senile plaques are derived by proteolytic cleavage from a larger protein that was called cleavage from a larger protein that was called amyloid precursor protein (APP). amyloid precursor protein (APP).

• The APP has a single transmembrane domain The APP has a single transmembrane domain and 3 isoforms with 695, 751, 770 amino and 3 isoforms with 695, 751, 770 amino acids.acids.

• Some of the APP molecules are found in the Some of the APP molecules are found in the membrane at the terminal ends of axons and membrane at the terminal ends of axons and other intracellular other intracellular membranesmembranes

Fig 14.9

Neurofibrillary tanglesNeurofibrillary tangles• The main fibrous elements are numerous paired The main fibrous elements are numerous paired

helical filaments (PHFs) which consist of 2 cross-helical filaments (PHFs) which consist of 2 cross-linked, intertwined protein strands with each linked, intertwined protein strands with each made up of joined tau protein molecules making made up of joined tau protein molecules making the tau filament.the tau filament.

• Tau protein binds to tubluin molecules and Tau protein binds to tubluin molecules and facilitates the assembly of tubulin into facilitates the assembly of tubulin into microtublules and maintains their stabilitymicrotublules and maintains their stability

• Tau molecules under abnormal conditions in the Tau molecules under abnormal conditions in the NFTs are hyperphophorylated. NFTs are hyperphophorylated.

• This cause them not to bind to tubulin but attache This cause them not to bind to tubulin but attache to other microtubule associated proteins.to other microtubule associated proteins.

• This is thought that the new tau molecules block This is thought that the new tau molecules block the formation of microtubules and undermine the the formation of microtubules and undermine the stability of existing microtubules.stability of existing microtubules.

ReferencesReferences

• Human molecular genetics.Hohn Human molecular genetics.Hohn Wiley & Sons, Inc., Hoboken , NJ. Wiley & Sons, Inc., Hoboken , NJ. 2005. pp 404-4082005. pp 404-408

• http://www.ahaf.org/alzdis/about/AmyloidPlaques.htm

• http://web.lemoyne.edu/~hevern/http://web.lemoyne.edu/~hevern/psy340/graphics/psy340/graphics/alzheimer.normal.brain.jpgalzheimer.normal.brain.jpg