Alzheimer’s disease (AD) characterized by two main features in the brain, an extracellular accumulation of beta-amyloid peptide (Aβ) into plaques and an intracellular buildup of neurofibrillary tangles made of a protein called tau. In addition, it has also been found that the brains of AD patients are continuously present in inflammatory states.

The neurofibrillary tangles are results of an accumulation in neuronal cells of tau protein that has been hyper-phosphorylated and self-assembled into a new form. The buildup of Aβ is a likely cause for the formation of the neurofibrillary tangles in Alzheimer’s patients.

Inflammation in the brain also has a possible link to the accumulation of Aβ. The Roskamp Institute has found that the binding of CD40 ligand (CD40L) to its receptor CD40 is harmful for AD. This proved to be true in a transgenic mouse model for AD TG2576, as prohibiting the binding of CD40-CD40L lessened Aβ buildup and the neuroinflammation.

In a study published in Brian Research, the Roskamp Institute reported findings that indicated that a decrease in the hyper-phosphorylation of the tau protein is not related to the accumulation of Aβ. A CD40 or CD40L deficiency in the mouse model for AD Tg2576 also decreased the hyper-phosphorylation of the tau protein, which implies that the CD40-CD40L pathway has a direct impact on tau phosphorylation.

These studies and findings indicate that the CD40-CD40L pathway has a direct effect on the two main characteristics of AD, which increases the possibility for it to be targeted in future therapeutic solutions.


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Wendy Liu

August 3, 2012



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