Alzheimer Disease By Ashley Wallace

Facts Discovered by Alois Alzheimer in 1907Discovered by Alois Alzheimer in /3 or more of all diagnosed cases of dementia are Alzheimer cases2/3 or more of all diagnosed cases of dementia are Alzheimer cases 100,000 people die each year from it100,000 people die each year from it 4 th leading cause of death after heart disease, cancer and stroke4 th 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.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 groupGenerally 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.Some other circumstances causing dementia include Huntington Disease, Parkinson Disease, head injury, multiple strokes, alcoholism, and others.

Symptoms of Alzheimer Disease 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 worsensAbility to concentrate and recall past events worsens Loss of accurate sense of time, and inability to relay the year, day or monthLoss of accurate sense of time, and inability to relay the year, day or month Sentence formation and coherent verbal communication diminishSentence formation and coherent verbal communication diminish Personality ChangePersonality Change 50% suffer from delusions50% suffer from delusions In the end AD patients are mute immobilized and uncomprehendingIn the end AD patients are mute immobilized and uncomprehending Death is often the result of respiratory failureDeath is often the result of respiratory failure

3 Neuropathological Features of an AD patients Brain 1.Devastating losses of synapses and neurons within the hippocampus and the entorhinal cortex. 2.Dense spherical structures called senile plaques are prevalent outside the neurons of the hippocampus and other regions of the brain. 3.Aggregations of fibrils called neurofibrillary tangles accumulate within the cell bodies and dendritic processes of the neurons of the hippocamupus.

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Senile Plaque Extracellular deposits of amyloid in the grey matter of the brain.Extracellular deposits of amyloid in the grey matter of the brain. The core is a densely packed fibrous structure that is called amyloid body.The core is a densely packed fibrous structure that is called amyloid body. These are mainly made up of protein.These are mainly made up of protein. Principle protein is a 4kDa peptide (ΑΒ protein; Β protein; Α4, Β/Α4).Principle protein is a 4kDa peptide (ΑΒ protein; Β protein; Α4, Β/Α4). ΑΒ protein consists of isoforms that range from amino acidsΑΒ protein consists of isoforms that range from amino acids There are at least 13 other proteins that form these that are associated with diseases that do not in any way resemble ADThere 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.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).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.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 membranesSome 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.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 stabilityTau 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.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 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.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 pp Human molecular genetics.Hohn Wiley & Sons, Inc., Hoboken, NJ pp ques.htm hics/alzheimer.normal.brain.jpghttp://web.lemoyne.edu/~hevern/psy340/grap hics/alzheimer.normal.brain.jpg