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How Alzheimer's Works (Sorta) - Coggle Diagram
How Alzheimer's Works (Sorta)
S100 Beta Protein
Beta-amyloid
Abnormal levels result in clumps of the protein
Plaques collect between neurons and disrupt cell function
Little correlation between overall plaque densisty and cognitive state (am; Green et al 2000)
Hyperphosphorylation:
Signalling mechanism used by cell to regulate mitosis.
Formed from the breakdown of larger protein:
APP
APP is metabolised by three secretase activities: alpha-secretase, beta-secretase or beta-amyloid cleaving enzyme (BACE), and gama-secretase(Allison et al. 2003
Source
Found in normal biological fluids throughout life. However, high levels become toxic
Source
(11 August)
Neurofibrillary Tangle
Deposits of insoluble and hyperphosphorylated tau protien
Plaques form where the cell body (or soma) connects to the axon. This is called the axonal hillock
Source
Neurons
Healthy Neurons
Supported by microtubiles
Help guide nutrients and molecules fromcell body to the axon and dendrites
Tau protiens bind to and stabilize microdutbules
Alzheimer's Neurons
Tau protiens detach from microtubules and stick to other tau molecules
Caused by abnormal chemical changes
These form threads that eventrually form tangles
Tangles block neuron's transport system
Harms synaptic communication between neurons
Earliest changes are an increase in tau phosphorlation and a redistribution of tau from the axon to the cell body
Synapse
Synaptogenesis
- synapse formation, maintenance, and refinment/elimination. Important for establisment of neural network
Source
(11 August).
Amyloid precursor Protein (APP)
production is increased during neuronal differentiation, maximal during snaptogensis, and declining when mature connections are established
Questions
Does APP play in a role in neural growth?
Fragile X mental redardation protein (FMRP)
FMRP levels decrease during synaptogenesis
Findings indicate FMRP levels decrease in an age-dependent manner
Real World Issues
'As a concsequence of increasing longevity in the oioulation the orevalence of dementia has risen and continues to rise alarmingly. It was estimated that in 1997 there were approximately 2.3 million persons wict dementia in the USA, with a further 360, 000 new casees arising anually' (Brookmeye et al. 1998)
Source
(12 August
Treatment
When first discovered, antibodies were developed that allowed the more subtle techniques of immunocytochemistry to be used on brain material. (Braak et al. 1989; Braak and Braak 1990, 1991)
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Cholinergic hypothesis led to an effort to design compounds to increase cholingergic function including precursor therapies such as lecithin, receptor agonist approaches and the cholinesterase inhibitors.
Cholinesterase inhibitors proved to be the first successful dug therapy to AD
The proteins that breakdown APP are obvious sites for therapeutic intervention.
BACE and its homologue BACE2 inhibitors hace been produced that might have potential as therapies to prevent amyloid formation (Potter & Dressler 2000)
Source
This is problematic because the center for disease control has estimated an increase in the people over the age of 65 from 420 million, in 2000, to 1 billion by 2030
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