Alzheimer's Disease

Alzheimer's disease is an age-related neurodegenerative disease that progresses over time. It is marked by amyloid deposits in the brain as well neurofibrillary tangles in neurons. These amyloid deposits are from amyloid precursor protein. Normally, APP is cleaved by α-secretase and then γ-secretase. Because α-secretase is first, it prevents Aβ from being formed. However, AD neurons see β-secretase enzyme as the one that cleaves APP, resulting in sAPPβ to be released from the cell. Cleavage by β and then γ-secretase results in Aβ40, Aβ42, and C99 amino acid peptide formation. Aβ42 concentration increases, which favors oligomer formation. These oligomers surround meningeal and cerebral vessels and gray matter, forming the plaques characteristic of Alzheimer’s disease.

The neurofibrillary tangles are because of over phosphorylation of Tau, which causes the Tau molecule to detach from microtubules in the neuron. The detached hyper-phosphorylated Tau molecules form filament structures (helical filaments). This causes build-up of neurofibrillary tangles. Few biomarkers for AD are reliable, but recent research has seen development of Aβ-PET markers. These markers allow one to see the Aβ plaque formation and increase. One new therapy being researched at the moment is aducanumab which targets amyloid β. More research is still forthcoming to better understand this neurodegenerative disease and eventually treat it.