AD set 4

cerebral hemispheres

connects two cerebral hemispheres

outer layer called cerebral cortex

• balance and coordination
• 10% of brain 
• 2 hemispheres
• receives info from eyes, ears and muscles about movements and position

• connects the spinal cord with brain
• relay messages to and from organs
• controls automatic function (heart rate, blood pressure, breathing)

short term memories to long term

receives sensory and limbic info and sends to cerebral cortex

neurotransmitters to monitor and control body functions (internal clock)

controls emotions and instinctive behavior

• positron emission tomography 
• pairs of gamma rays emitted by tracer (fludeoxyglucose, glucose analogue) detected as a function of position and time, thus signaling metabolic activity

myelin content (lipids vs free and bound water)

• extreme shrinkage in hippocampus and cerebral cortex
• enlarged ventricles

• long ago memories
• confabulation
• emotional memories
• motor memories

• can get facial expression
• hears tone of voice
• gets some non-verbal cues

• singing
• automatic speech
• swearing

desires to be respected, in control and regrets after action

outside and around nerve cells

twisted fibers that build up inside nerve cell

phosphorylated tau

stabilizes microtuble, part of cell's transport system

one pass TM protein in neurons

becomes hyperphosphorylated (MT collapse) and assemble into spirals (PHF) which forms NFT that lead to cell death

• AB leads to hyperphosphorylation of tau
• tau mediates AB toxicity
• ab and tau act together, amplifying individual toxcities

• initiation of ab formation in brain (MCI)
• low levels of denderitic tau are associated with limited vulnerability of neurons to synaptic amyloid beta toxicity
• ab induced toxicity causes high phos tau in neurons as disease progresses (tau increase in dendrite)
• progressively increasing levels of dendritic tau make neurons vulnerable to b-amyloid toxicity in postsynaptic compartment
• which further increase tau phos and somatodendritic accumulation (cycle)

4kDA

• free radicals (oxidative damage)-> neuronal injury
• homocysteine increased in AD (also in heart diseases)
• inflammation and strokes

• cells are shrinking and dying
• cells are producing less chemicals to send messages

• loss of neurons results in less NT
• greater distance between cells
• AChE hydrolyze them before sufficient number of ACh molecules can deliver their message

• baptists
• tauists

amyloid b42 accumulation leads to formation of plaques

phis makes them sticky, break up of MT, loss of axonal transport causes death

• APP broken down
• nonsoluble fragment (AB42 accumulates) and deposited outside the cell
• plaques

presenilins (subunits of y-secretase)

neuronal growth, survival and repair

• B-secretase (outside)
• y-(in membrane)

self aggregate and attracts other materials to form plaque

A673V

blood level increase in AB, weakening of cerebral blood vessels, more diffuse plaques

• several mutations in APP gene on chromosome 1
• most common Val717Iso
• abnormal ab fragment
• 15-20% fAD
• autosomal dominant

• mutations in PSEN1 on chromosome 14
• lead to aa substitution
• overproduction of ab fragment
• 30-70 fAD

• mutations in PSEN2 on chromosome 1
• 2 alleles (Asn141Iso and Met239Val)
• overproduction of ab fragment
• less 5% fAD

• epsilon 4 allele of ApoE gene on chromosome 19 confers risk
• epsilon 2 of ApoE gene on chromosome 19 confers protection
• unclear mechanism
• ApoE is very low density lipoprotein that transports cholesterol
• most cases are late

• delay onset of AD pathology
• decrease ab 42 production
• prevent tangle formation

• delay onset of MCI individuals with pathology
• decrease accumulated ab burden
• decrease neurodegeneration with anti-tau or neuroprotective agents

• delay onset or progression of dementia
• neuroprotection-prevent neuronal loss
• enhance function of remaining neurons
• neurotransmitter repletion