Abstract

Alzheimer’s disease (AD) is distinguished by two major pathologies found in post-mortem AD patients:  plaques and tangles.  Plaques are found outside of neurons, specifically around the connecting fibers called dendrites.  Tangles are found inside the cell body.  Both pathologies cause damage to neurons by promoting stress that eventually results in cell death.  Plaques and tangles are both formed when proteins within neurons malfunction.  One such protein, amyloid precursor protein (APP), is a transmembrane protein believed to transport iron out of the cell.  A non-AD brain cleaves this protein and produces a p3 peptide that is recognized and degraded normally.  When an APP mutation occurs, such as in the case of AD, APP is cleaved incorrectly resulting in a larger peptide fragment, Aβ, which cannot be degraded.  These Aβ fragments accumulate and form the plaques that cause neuron damage.  Alternatively, tangles are caused by problems with a different protein called tau.  Tau is involved in the construction of microtubules, which serve as an important part of the cytoskeleton.  Proper phosphorylation of tau regulates the assembly of microtubules, which are important in transport and structure within neurons.  However, in AD, tau is hyper-phosphorylated which causes the microtubules to fall apart.  This causes tau to build up inside the cell causing tangles to form.  Therefore, the accumulation of Aβ and tau play a critical role in promoting AD, but questions still remain about their role in both the genesis and unfolding of the disease.

 

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These authors made this poster for Biology 362: Mechanisms of Brain Dysfunction taught by Dr. Shubhik DebBurman.