Neuropathology of Alzheimer's Disease Flashcards
State the 2 pathological causes of Alzheimer’s Disease (AD).
Beta amyloid plaques. Neurofibrillary tangles.
What is the function of the amyloid precursor protein (AP)?
Helps neuron grow and repair. Gets used, broken down and recycled.
Amyloid precursor protein is normally degraded by which 2 enzymes?
Alpha and gamma secretase.
What is the danger of beta secretase degrading amyloid precursor protein?
Abnormal APP is insoluble, therefore clumps up around neurones - forms a beta amyloid plaque.
State the three dangers of beta amyloid plaques.
Plaques get between neurones, to effect stimulation. Plaque clumps around neurones affecting inflammation. Clumps can weaken blood vessels - haemorrhage. Beta amyloid plaque activates kinase.
What is the effect of phosphate on Tau?
Tau protein changes shape and clumps - produce neurofibrillary tangles.
What is the function of Tau proteins?
They keep microtubules intact.
Where do neurofibrillary tangles develop, inside or outside neurones?
Inside.
Does the Sulci or Gyri widen during AD?
Sulci.
What happens to the size of the ventricles during AD?
They enlarge.
What happens to the brain during AD?
Brain atrophy (shrinks).
What late onset genes are connected with AD?
Apolipoprotein E (APOEe4 gene) - e4 allele.
Which 2 genes are are linked to late onset AD?
Presinilin - 1 (PSEN-1) . Presinilin - 2 (PSEN-2).
How does presenilin affect gamma secretase subunits?
They cause gamma secretase to cut APP at a different point - abnormal APP.
Name a syndrome associated with late onset AD.
Down’s Syndrome.
State a characteristic of early stage AD.
Impaired memory. Loss of motivation. Loss of concentration. Handling complex tasks impaired.
State a characteristic of intermediate stage AD.
Apathetic. Aggression. Agitation. Impaired language function. Remote memory loss (
State a characteristic of advanced stage AD.
Complete debilitation - dependence on others (urinary incontinence).
State 2 ways to diagnose AD.
CT scan/MRI - hippocampus atrophy, sulci widening, gyri narrowing. Mental state scale clinical assessment. Post-autopsy brain biopsy.
State 2 ways to treat AD.
Acetylcholinesterase inhibitors. Vitamin E supplements. Memantine (advanced stages).
